Osteoarthritis
Conditions
Keywords
Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases
Brief summary
Nearly one out of every two Americans will develop knee osteoarthritis by age 85. Over 20 million Americans, including nearly three million Veterans, currently have painful knee arthritis that limits their daily activity or recreation. The vast majority of those individuals will be prescribed anti-inflammatory drugs that provide some pain relief but do not slow the progression of the disease. Often people with knee arthritis are told they must live with the pain until they become appropriate candidates for knee replacement surgery, but that can require tolerating the pain and limiting function for many years. Because of other health issues, some individuals are never acceptable surgery candidates. What is desperately needed are better conservative approaches for treating these patients. Two such approaches will be tested and compared in this study.
Detailed description
This study is a randomized controlled trial to investigate conservative treatments for individuals with painful knee osteoarthritis (OA). The study will recruit participants who have isolated, medial compartment knee OA. Subjects will be assigned to one of two gait training groups. Both groups will undergo gait analysis to determine their foot progression angle at their comfortable walking speed. Both groups will receive personalized gait retraining to either alter their foot progression angle or to achieve consistency of their natural foot progression angle. Gait retraining will consist of once a week sessions for six weeks. The gait training will use a fading feedback approach, where the percentage of each weekly session during which feedback is used is decreased from week to week until no feedback is used by the last training session. Throughout the six-week training period subjects will be encouraged to practice their gait for at least ten minutes per day. Subjects will continue to practice their gait throughout the remainder of the 52-week intervention. Subjects will have their walking activity recorded using a 3-axis pedometer. Compared to their baseline walking activity, participants will be instructed to increase their daily walking by ten minutes per day throughout the 52-week intervention. All subjects will receive monthly phone calls to encourage maintaining a regular walking regimen. Walking activity will be monitored periodically using a pedometer. Subjects will receive knee MRIs and weight-bearing knee radiographs at the start and end of the study. All participants will complete pain evaluations and clinical knee score questionnaires during the study. The investigators expect that subjects in both groups will have a reduction in knee pain over the course of the 52-week intervention. The primary objective of the study it to determine if the change in pain between baseline and week 52 is different between the two groups.
Interventions
OTHERGait Training; Altered Foot Progression Angle
Participants will receive personalized gait training while walking on a treadmill with real-time, haptic feedback to encourage them to adopt a new foot progression angle. Participants will walk for an additional ten minutes per day to internalize their new foot progression angle over 52 weeks.
OTHERGait Training; Consistent Foot Progression Angle
Participants will receive personalized gait training while walking on a treadmill with haptic feedback to encourage them to maintain a consistent foot progression angle. Participants will walk an additional ten minutes per day to internalize the consistency of their foot progression angle over 52 weeks.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with isolated, medial compartment knee OA of at least six months duration * Kellgren-Lawrence grade of I, II, or III * Age greater than 18 years at the time of enrollment * Ability to give informed consent * Knee pain more than three days per week on average * Average knee pain in medial compartment between 3 and 9 on an 11-point Numerical Rating Scale, and greater than pain in other compartments * Ambulatory without aids * Able to walk for at least 25 consecutive minutes * Able to walk on treadmill safely at 0.7 m/s or faster * Able to reduce the prominent peak of the knee adduction moment by changing foot progression angle
Exclusion criteria
* Body mass index equal to or greater than 35 * Pregnancy * Plans for knee replacement within the next 12 months * Contraindications to MRI * Nerve or muscle disease associated with walking difficulty * Narcotic pain medication usage * History of rheumatoid arthritis or autoimmune disease * An episode of gout or pseudogout in the knee in the past year * History of neuropathic arthropathy, infectious disease, or other major systemic diseases * Current or recent past use (within two months) of oral corticosteroids * Cognitive impairments that would limit a subject's understanding * Expecting a significant change in activity level or weight within the next 12 months * Regularly participates in high impact activities such as running, soccer, basketball, etc. * Unable to perform the 3rd stage of the 4-stage balance test, which involves holding a tandem stance for 10 seconds The following criteria apply only to the affected osteoarthritic limb: * History of symptomatic arthritis in lower limb joints other than the knees that is more severe than knee arthritis * Replacement of any lower extremity joint * Lateral tibiofemoral joint space width less than medial * Recurrent giving way of the knee * Symptoms arising primarily from a meniscal or ligament pathology or other structure not directly related to osteoarthritis as identified by physical exam, health record, or MRI * Symptoms originating primarily from the patellofemoral joint * Avascular necrosis * Recent (within two months) knee injury or surgery * Planned use of hinged knee brace in next 12 months * Severe knee malalignment of more than 10 degrees from neutral * Intra-articular injection within the past 2 months or planned for the next 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Medial Knee Pain | Baseline and Week 52 | Change in medial knee pain between baseline and week 52 using an 11-point Numeric Rating Scale (NRS) to assess average medial knee pain over the past 7 day period. Possible scores range from 0 (no pain) to 10 (worst pain imaginable). Change = (Week 52 score - Baseline score). |
| Change in Knee Adduction Moment | Baseline and Week 52 | Change in magnitude of the more prominent peak in the knee adduction moment (KAM), a surrogate measure for medio-lateral load distribution in the knee, between baseline and week 52. A reduction in KAM indicates a shift in loading from the medial to the lateral compartment of the knee. Change = (Week 52 - Baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Medial T1rho Relaxation Time | Baseline and Week 52 | Change in T1rho relaxation time measured from quantitative MRI in the medial compartment of the knee between baseline and week 52. T1ρ relaxation time is sensitive to changes in proteoglycan content in the articular cartilage. Increased values of T1rho indicate increased depletion of proteoglycans and increased cartilage degeneration. Change = (Week 52 - Baseline). |
| Change in Medial T2 Relaxation Time | Baseline and Week 52 | Change in T2 relaxation time measured from quantitative MRI in the medial compartment of the knee between baseline and week 52. T2 relaxation time is sensitive to changes in water content and collagen matrix integrity of the articular cartilage. Increased values of T2 indicate increased cartilage degeneration. Change = (Week 52 - Baseline). |
| Change in Lateral T1rho Relaxation Time | Baseline and Week 52 | Change in T1rho relaxation time measured from quantitative MRI in the lateral compartment of the knee between baseline and week 52. T1ρ relaxation time is sensitive to changes in proteoglycan content in the articular cartilage. Increased values of T1rho indicate increased depletion of proteoglycans and increased cartilage degeneration. Change = (Week 52 - Baseline). |
| Change in Lateral T2 Relaxation Time | Baseline and Week 52 | Change in T2 relaxation time measured from quantitative MRI in the lateral compartment of the knee between baseline and week 52. T2 relaxation time is sensitive to changes in water content and collagen matrix integrity of the articular cartilage. Increased values of T2 indicate increased cartilage degeneration. Change = (Week 52 - Baseline). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited via clinician referrals, approved searches of medical record databases, and advertisements in print media and online. The first participant was enrolled in August 2016 and the last participant was enrolled in June 2019.
Pre-assignment details
Interested individuals were initially screened via telephone or web-based questionnaire. Eligible individuals then underwent an in-person screen to confirm the location and severity of knee pain. Anterior-posterior weightbearing radiographs were obtained and given a KL grade. Participants who met the radiographic inclusion criteria were invited to the motion laboratory for a gait assessment. Those who were able to reduce their KAM peak by at least 5% with an FPA modification were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Gait Training; Altered Foot Progression Angle Participants will receive personalized gait training while walking on a treadmill with real-time, haptic feedback. The goal of the training is to encourage participants to adopt an altered foot progression angle in an attempt to alter the distribution of forces crossing the knee joint. Training will occur once a week for six weeks. This will be followed by a 46-week home and community-based walking program to practice and internalize the new personalized, gait pattern and to encourage daily walking. Refresher training with haptic feedback will be offered at weeks 11, 25 and 39 to enhance internalization of the new foot progression angle.
Gait Training; Altered Foot Progression Angle: Participants will receive personalized gait training while walking on a treadmill with real-time, haptic feedback to encourage them to adopt a new foot progression angle. Participants will walk for an additional ten minutes per day to internalize their new foot progression angle over 52 weeks. | 34 |
| Gait Training; Consistent Foot Progression Angle Participants will receive personalized gait training while walking on a treadmill with haptic feedback. The goal of the training is to encourage participants to maintain a consistent foot progression angle in an attempt to minimize the variability in the forces crossing the knee joint. Training will occur once a week, for 6 weeks. This will be followed by a 46-week home and community-based walking program to encourage daily walking. Refresher training with haptic feedback will be offered at weeks 11, 25 and 39 to maintain foot progression angle consistency.
Gait Training; Consistent Foot Progression Angle: Participants will receive personalized gait training while walking on a treadmill with haptic feedback to encourage them to maintain a consistent foot progression angle. Participants will walk an additional ten minutes per day to internalize the consistency of their foot progression angle over 52 weeks. | 34 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | COVID shutdown | 2 | 5 |
| Overall Study | Increased pain | 2 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Received intra-articular injection | 0 | 1 |
| Overall Study | Unrelated medical issue | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Gait Training; Altered Foot Progression Angle | Gait Training; Consistent Foot Progression Angle | Total |
|---|---|---|---|
| Age, Continuous | 64.32 years STANDARD_DEVIATION 7.66 | 64.53 years STANDARD_DEVIATION 7.63 | 64.43 years STANDARD_DEVIATION 7.59 |
| Body Mass Index | 25.53 kg/m^2 STANDARD_DEVIATION 3.26 | 27.37 kg/m^2 STANDARD_DEVIATION 3.95 | 26.45 kg/m^2 STANDARD_DEVIATION 3.71 |
| Daily steps | 6343 steps/day STANDARD_DEVIATION 2678 | 6280 steps/day STANDARD_DEVIATION 3073 | 6311 steps/day STANDARD_DEVIATION 2860 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 34 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| KAM peak, natural FPA | 3.25 %Bodyweight*Height STANDARD_DEVIATION 1.05 | 3.30 %Bodyweight*Height STANDARD_DEVIATION 1.05 | 3.27 %Bodyweight*Height STANDARD_DEVIATION 1.04 |
| KAM peak, target FPA | 2.87 %Bodyweight*Height STANDARD_DEVIATION 1.05 | 3.30 %Bodyweight*Height STANDARD_DEVIATION 1.05 | 3.08 %Bodyweight*Height STANDARD_DEVIATION 1.06 |
| Kellgren-Lawrence classification of knee OA Grade 1 | 7 Participants | 7 Participants | 14 Participants |
| Kellgren-Lawrence classification of knee OA Grade 2 | 14 Participants | 17 Participants | 31 Participants |
| Kellgren-Lawrence classification of knee OA Grade 3 | 13 Participants | 10 Participants | 23 Participants |
| NRS pain, medial | 4.32 units on a scale STANDARD_DEVIATION 1.32 | 4.00 units on a scale STANDARD_DEVIATION 1.21 | 4.16 units on a scale STANDARD_DEVIATION 1.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 28 Participants | 26 Participants | 54 Participants |
| Region of Enrollment United States | 34 Participants | 34 Participants | 68 Participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
| WOMAC function | 75.74 units on a scale STANDARD_DEVIATION 14.23 | 73.17 units on a scale STANDARD_DEVIATION 13.06 | 74.45 units on a scale STANDARD_DEVIATION 13.62 |
| WOMAC pain | 70.74 units on a scale STANDARD_DEVIATION 12.86 | 71.21 units on a scale STANDARD_DEVIATION 11.18 | 70.97 units on a scale STANDARD_DEVIATION 11.97 |
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
Primary
Change in Knee Adduction Moment
Change in magnitude of the more prominent peak in the knee adduction moment (KAM), a surrogate measure for medio-lateral load distribution in the knee, between baseline and week 52. A reduction in KAM indicates a shift in loading from the medial to the lateral compartment of the knee. Change = (Week 52 - Baseline).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Knee Adduction Moment | -0.17 %Bodyweight*Height | Standard Deviation 0.47 |
| Gait Training; Consistent Foot Progression Angle | Change in Knee Adduction Moment | 0.08 %Bodyweight*Height | Standard Deviation 0.33 |
p-value: <0.00195% CI: [-0.39, -0.13]Regression, Linear
Primary
Change in Medial Knee Pain
Change in medial knee pain between baseline and week 52 using an 11-point Numeric Rating Scale (NRS) to assess average medial knee pain over the past 7 day period. Possible scores range from 0 (no pain) to 10 (worst pain imaginable). Change = (Week 52 score - Baseline score).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Medial Knee Pain | -2.5 score on a scale | Standard Deviation 2.2 |
| Gait Training; Consistent Foot Progression Angle | Change in Medial Knee Pain | -1.3 score on a scale | Standard Deviation 2.3 |
Comparison: For the primary hypothesis that there would be a greater reduction in pain for the altered compared to the consistent FPA group, an effect size of 0.57 was assumed. To achieve 80% power with an alpha of 0.05, 39 participants per group were needed, so our recruitment goal was 40 subjects per group.p-value: 0.00195% CI: [-1.9, -0.5]Regression, Linear
Secondary
Change in Lateral T1rho Relaxation Time
Change in T1rho relaxation time measured from quantitative MRI in the lateral compartment of the knee between baseline and week 52. T1ρ relaxation time is sensitive to changes in proteoglycan content in the articular cartilage. Increased values of T1rho indicate increased depletion of proteoglycans and increased cartilage degeneration. Change = (Week 52 - Baseline).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Lateral T1rho Relaxation Time | -1.11 ms | Standard Deviation 6.07 |
| Gait Training; Consistent Foot Progression Angle | Change in Lateral T1rho Relaxation Time | -0.83 ms | Standard Deviation 6.8 |
p-value: 0.8595% CI: [-3.38, 2.8]Regression, Linear
Secondary
Change in Lateral T2 Relaxation Time
Change in T2 relaxation time measured from quantitative MRI in the lateral compartment of the knee between baseline and week 52. T2 relaxation time is sensitive to changes in water content and collagen matrix integrity of the articular cartilage. Increased values of T2 indicate increased cartilage degeneration. Change = (Week 52 - Baseline).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Lateral T2 Relaxation Time | -0.02 ms | Standard Deviation 2.14 |
| Gait Training; Consistent Foot Progression Angle | Change in Lateral T2 Relaxation Time | -0.02 ms | Standard Deviation 1.88 |
p-value: 0.9995% CI: [-0.89, 0.9]Regression, Linear
Secondary
Change in Medial T1rho Relaxation Time
Change in T1rho relaxation time measured from quantitative MRI in the medial compartment of the knee between baseline and week 52. T1ρ relaxation time is sensitive to changes in proteoglycan content in the articular cartilage. Increased values of T1rho indicate increased depletion of proteoglycans and increased cartilage degeneration. Change = (Week 52 - Baseline).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Medial T1rho Relaxation Time | -1.72 ms | Standard Deviation 5.68 |
| Gait Training; Consistent Foot Progression Angle | Change in Medial T1rho Relaxation Time | 2.02 ms | Standard Deviation 5.53 |
p-value: 0.00695% CI: [-6.42, -1.05]Regression, Linear
Secondary
Change in Medial T2 Relaxation Time
Change in T2 relaxation time measured from quantitative MRI in the medial compartment of the knee between baseline and week 52. T2 relaxation time is sensitive to changes in water content and collagen matrix integrity of the articular cartilage. Increased values of T2 indicate increased cartilage degeneration. Change = (Week 52 - Baseline).
Time frame: Baseline and Week 52
Population: Intent-to-treat population. Missing data were imputed using the Markov chain Monte Carlo method for continuous variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gait Training; Altered Foot Progression Angle | Change in Medial T2 Relaxation Time | -0.58 ms | Standard Deviation 2.65 |
| Gait Training; Consistent Foot Progression Angle | Change in Medial T2 Relaxation Time | -0.52 ms | Standard Deviation 3.11 |
p-value: 0.9395% CI: [-1.42, 1.3]Regression, Linear