Anterior Cruciate Ligament Injuries, Knee Osteoarthritis
Conditions
Brief summary
Fifty percent of teenagers and young adults who suffer an anterior cruciate ligament (ACL) injury develop knee osteoarthritis (OA) within 15 years. The resulting pain, reduced quality-of-life, and increased risk for co-morbidity lead to substantial healthcare costs, inability to fulfill work and personal responsibilities, and reduced long-term health. Degeneration in articular cartilage, connective tissue that covers the ends of bones in the knee, is the hallmark of early OA development after knee injury. This deterioration can be measured by an imaging biomarker for OA development on quantitative magnetic resonance imaging (MRI). Harmful increases in MRI markers of the knee's articular cartilage occur within months of ACL injury and indicate preventative interventions should begin soon after injury. However, evidence-based interventions to prevent OA do not exist. This project will challenge the traditional OA paradigm that too much joint loading (e.g. "wear and tear") causes cartilage breakdown. A multi-disciplinary team has developed a novel visual biofeedback paradigm using portable force plates that can increase knee loading during squats within a single session after ACL reconstruction (ACLR). This study will determine the efficacy of the visual biofeedback program initiated two weeks after ACLR by assessing movement biomechanics and MRI changes in cartilage after six months later. Successful completion of this project will establish the first rehabilitation intervention to effectively and optimally load the knee joint early after ACLR, providing the initial steps to prevent OA after ACL injury.
Detailed description
Fifty percent of teenagers and young adults who suffer an anterior cruciate ligament (ACL) injury develop radiographic knee osteoarthritis (OA) within 15 years. The resulting pain, reduced quality-of-life, and increased risk for co-morbidity lead to substantial healthcare costs, inability to fulfill work and personal responsibilities, and reduced long-term health. Degeneration in articular cartilage, connective tissue that covers the ends of bones in the knee, is the hallmark of early OA development after knee injury. This deterioration can be measured by increased T2 and T1rho relaxation time on quantitative magnetic resonance imaging (MRI), an imaging biomarker for OA development. Harmful increases in MRI markers of the knee's articular cartilage occur within months of ACL injury and indicate preventative interventions should begin soon after injury. However, evidence-based interventions to prevent OA do not exist. The investigators have shown that after ACL reconstruction (ACLR), patients exhibit asymmetric movement patterns characterized by up to 62% lower knee joint loading during walking and squatting in the injured limb at two months after ACLR. These knee joint loading patterns remain 40% lower at six months. Emerging evidence suggests knee joint unloading patterns after ACL injury may increase the risk for OA development. Currently, no studies have examined the efficacy of movement-focused interventions during the first months after ACLR, which explains the lack of evidence-based interventions that successfully increase knee loading early after ACLR. This gap presents a barrier to the long-term goal of preventing OA in young, active individuals before irreversible knee degeneration occurs. This project will challenge the traditional OA paradigm that too much joint loading (e.g. "wear and tear") causes cartilage breakdown. The multi-disciplinary team spanning rehabilitation, orthopaedics, radiology and biomechanics has developed a novel visual biofeedback paradigm using portable force plates that can increase knee loading during squats within a single session after ACLR. This data suggest movement is modifiable using visual feedback, but its efficacy beyond a single training session is unknown. This study will determine the efficacy of the visual biofeedback program initiated two weeks after ACLR by assessing movement biomechanics and MRI changes in cartilage microstructure six months later. Successful completion of this project will establish the first rehabilitation intervention to effectively and optimally load the knee joint early after ACLR, providing the initial steps in the team's work to prevent OA after ACL injury.
Interventions
PROCEDURESquat Biofeedback
The intervention group will complete bilateral squats with each limb on a separate portable force plate. They will receive real-time visual feedback on a 32-inch screen during all squats. Biofeedback conditions will be progressed from simplest (ground reaction force only) to most complex (ground reaction force plus center of pressure). This intervention will be included in additional to standard care post-operative physical therapy.
PROCEDUREStandard Care
The intervention group will receive standard care post-operative physical therapy.
Sponsors
University of Nebraska
National Institute of General Medical Sciences (NIGMS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Acute anterior cruciate ligament (ACL) injury in the past 6 months * ACL reconstruction in the past month or have a planned ACL reconstruction
Exclusion criteria
* Previous knee injury or surgery (contralateral knee) * Body mass index (BMI) over 35 kg/m2 * Concomitant posterior cruciate ligament reconstruction or cartilage procedure that includes extended weight bearing restrictions and/or changes to cartilage structure * Current or planned pregnancy during study duratuiom
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Knee Flexion Moment Impulse | Immediately post-intervention (within approximately 1 week after completing intervention) | Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the knee flexion moment impulse during descent and ascent of bilateral squatting was analyzed at post-intervention. A value of 1 represents symmetric knee flexion moment impulse; a value less than 1 represents a smaller knee flexion moment impulse in the injured compared to uninjured limb. |
| Cartilage T2 Relaxation Time | Baseline (immediately before intervention, 2-6 weeks after anterior cruciate ligament reconstruction) and 6 months after anterior cruciate ligament reconstruction. | Percent change in cartilage T2 relaxation time will be measured by a magnetic resonance imaging (MRI) scan. A positive percent change represents longer (worse) T2 relaxation times at 6 months compared to baseline testing. The cartilage region reported is the weightbearing area of the medial femoral condyle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Flexion Moment Impulse | 6 months after anterior cruciate ligament reconstruction. | Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the knee flexion moment impulse during descent and ascent of bilateral squatting was analyzed at 6 months. A value of 1 represents symmetric knee flexion moment impulse; a value less than 1 represents a smaller knee flexion moment impulse in the injured compared to uninjured limb. |
| Vertical Ground Reaction Force Impulse | Immediately post-intervention (approximately 1 week after intervention) | Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The vertical ground reaction force impulse was calculated. The interlimb ratio (injured limb / uninjured limb) of the vertical ground reaction force impulse during descent and ascent of bilateral squatting was analyzed at post-intervention. A value of 1 represents symmetric vertical ground reaction force impulse; a value less than 1 represents a smaller vertical ground reaction force impulse in the injured compared to uninjured limb. |
| Peak Knee Flexion Moment | Immediately post-intervention (within approximately 1 week after completing intervention) | Participants completed 5 valid trials of walking in each limb. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the peak knee flexion moment during walking was analyzed at post-intervention. A value of 1 represents symmetric peak knee flexion moment; a value less than 1 represents a smaller peak knee flexion moment in the injured compared to uninjured limb. |
| Quadriceps Strength | Immediately post-intervention (within approximately 1 week after completing intervention) | Participants completed 3 trials of maximal isometric quadriceps strength testing using an isokinetic dynamometer at each limb, with the best trial in each limb used for analysis. The interlimb ratio (injured limb / uninjured limb) of maximum quadriceps strength was analyzed at post-intervention. A value of 1 represents symmetric quadriceps strength; a value less than 1 represents less quadriceps strength in the injured compared to uninjured limb. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORElizabeth A Wellsandt, DPT, PhD
University of Nebraska
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biofeedback Group Provided real-time visual feedback on a screen during bilateral squat intervention. | 16 |
| Control Group Provided standard verbal instructions during bilateral squat intervention. | 17 |
| Total | 33 |
Baseline characteristics
| Characteristic | Control Group | Total | Biofeedback Group |
|---|---|---|---|
| Age, Continuous | 19.3 Years STANDARD_DEVIATION 4.6 | 20.1 Years STANDARD_DEVIATION 5.6 | 20.9 Years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Knee Flexion Moment Impulse at Baseline | 0.26 Ratio STANDARD_DEVIATION 0.16 | 0.25 Ratio STANDARD_DEVIATION 0.18 | 0.23 Ratio STANDARD_DEVIATION 0.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 10 Participants |
| Sex: Female, Male Male | 12 Participants | 17 Participants | 5 Participants |
| Vertical Ground Reaction Force Impulse at Baseline | 0.72 Ratio STANDARD_DEVIATION 0.12 | 0.72 Ratio STANDARD_DEVIATION 0.11 | 0.72 Ratio STANDARD_DEVIATION 0.11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 |
| other Total, other adverse events | 0 / 15 | 0 / 17 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 |
Outcome results
Primary
Cartilage T2 Relaxation Time
Percent change in cartilage T2 relaxation time will be measured by a magnetic resonance imaging (MRI) scan. A positive percent change represents longer (worse) T2 relaxation times at 6 months compared to baseline testing.
Time frame: Baseline (immediately before intervention, 2-6 weeks after anterior cruciate ligament reconstruction) and 6 months after anterior cruciate ligament reconstruction.
Primary
Knee Flexion Moment Impulse
Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the knee flexion moment impulse during descent and ascent of bilateral squatting was analyzed at post-intervention. A value of 1 represents symmetric knee flexion moment impulse; a value less than 1 represents a smaller knee flexion moment impulse in the injured compared to uninjured limb.
Time frame: Immediately post-intervention (within approximately 1 week after completing intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biofeedback Group | Knee Flexion Moment Impulse | 0.54 Ratio | Standard Deviation 0.28 |
| Control Group | Knee Flexion Moment Impulse | 0.50 Ratio | Standard Deviation 0.21 |
p-value: 0.293ANCOVA
Secondary
Knee Flexion Moment Impulse
Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the knee flexion moment impulse during descent and ascent of bilateral squatting was analyzed at 6 months. A value of 1 represents symmetric knee flexion moment impulse; a value less than 1 represents a smaller knee flexion moment impulse in the injured compared to uninjured limb.
Time frame: 6 months after anterior cruciate ligament reconstruction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biofeedback Group | Knee Flexion Moment Impulse | 0.66 Ratio | Standard Deviation 0.24 |
| Control Group | Knee Flexion Moment Impulse | 0.54 Ratio | Standard Deviation 0.21 |
p-value: 0.114ANCOVA
Secondary
Peak Knee Flexion Moment
Participants completed 5 valid trials of walking in each limb. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the peak knee flexion moment during walking was analyzed at post-intervention. A value of 1 represents symmetric peak knee flexion moment; a value less than 1 represents a smaller peak knee flexion moment in the injured compared to uninjured limb.
Time frame: Immediately post-intervention (within approximately 1 week after completing intervention)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biofeedback Group | Peak Knee Flexion Moment | 0.6 Ratio |
| Control Group | Peak Knee Flexion Moment | 0.7 Ratio |
p-value: 0.936Wilcoxon (Mann-Whitney)
Secondary
Peak Knee Flexion Moment
Participants completed 5 valid trials of walking in each limb. The external knee flexion moment was calculated using an inverse dynamics approach. The interlimb ratio (injured limb / uninjured limb) of the peak knee flexion moment during walking was analyzed at 6 months. A value of 1 represents symmetric peak knee flexion moment; a value less than 1 represents a smaller peak knee flexion moment in the injured compared to uninjured limb.
Time frame: 6 months after anterior cruciate ligament reconstruction.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biofeedback Group | Peak Knee Flexion Moment | 0.7 Ratio |
| Control Group | Peak Knee Flexion Moment | 0.7 Ratio |
p-value: 0.867Wilcoxon (Mann-Whitney)
Secondary
Quadriceps Strength
Participants completed 3 trials of maximal isometric quadriceps strength testing using an isokinetic dynamometer at each limb, with the best trial in each limb used for analysis. The interlimb ratio (injured limb / uninjured limb) of maximum quadriceps strength was analyzed at 6 months. A value of 1 represents symmetric quadriceps strength; a value less than 1 represents less quadriceps strength in the injured compared to uninjured limb.
Time frame: 6 months after anterior cruciate ligament reconstruction.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biofeedback Group | Quadriceps Strength | 0.8 Ratio |
| Control Group | Quadriceps Strength | 0.6 Ratio |
p-value: 0.379Wilcoxon (Mann-Whitney)
Secondary
Quadriceps Strength
Participants completed 3 trials of maximal isometric quadriceps strength testing using an isokinetic dynamometer at each limb, with the best trial in each limb used for analysis. The interlimb ratio (injured limb / uninjured limb) of maximum quadriceps strength was analyzed at post-intervention. A value of 1 represents symmetric quadriceps strength; a value less than 1 represents less quadriceps strength in the injured compared to uninjured limb.
Time frame: Immediately post-intervention (within approximately 1 week after completing intervention)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biofeedback Group | Quadriceps Strength | 0.5 Ratio |
| Control Group | Quadriceps Strength | 0.5 Ratio |
p-value: 0.37Wilcoxon (Mann-Whitney)
Secondary
Vertical Ground Reaction Force Impulse
Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The vertical ground reaction force impulse was calculated. The interlimb ratio (injured limb / uninjured limb) of the vertical ground reaction force impulse during descent and ascent of bilateral squatting was analyzed at post-intervention. A value of 1 represents symmetric vertical ground reaction force impulse; a value less than 1 represents a smaller vertical ground reaction force impulse in the injured compared to uninjured limb.
Time frame: Immediately post-intervention (approximately 1 week after intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biofeedback Group | Vertical Ground Reaction Force Impulse | 0.91 Ratio | Standard Deviation 0.08 |
| Control Group | Vertical Ground Reaction Force Impulse | 0.84 Ratio | Standard Deviation 0.11 |
p-value: 0.017ANCOVA
Secondary
Vertical Ground Reaction Force Impulse
Participants completed 3 sets of 5 bilateral bodyweight squats with arms crossed at the chest, with the middle 3 of each set (9 total) averaged and reported. The vertical ground reaction force impulse was calculated. The interlimb ratio (injured limb / uninjured limb) of the vertical ground reaction force impulse during descent and ascent of bilateral squatting was analyzed at 6 months. A value of 1 represents symmetric vertical ground reaction force impulse; a value less than 1 represents a smaller vertical ground reaction force impulse in the injured compared to uninjured limb.
Time frame: 6 months after anterior cruciate ligament reconstruction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biofeedback Group | Vertical Ground Reaction Force Impulse | 0.95 N/A (Ratio) | Standard Deviation 0.08 |
| Control Group | Vertical Ground Reaction Force Impulse | 0.86 N/A (Ratio) | Standard Deviation 0.1 |
p-value: 0.021ANCOVA