Anterior Cruciate Ligament Injuries, Exercise, Cartilage, Articular, Knee Injuries, Osteoarthritis, Osteoarthritis, Knee, Arthritis, Joint Diseases
Conditions
Brief summary
Osteoarthritis (OA) is a leading cause of disability worldwide that affects millions of Americans each year. Posttraumatic OA (PTOA) significantly impacts patients after anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) with approximately 50% of patients developing PTOA within 20 years of injury or surgery. Knee joint mechanical loading measured via physical activity (i.e. daily steps) is insufficient in individuals after ACLR compared to uninjured individuals. Establishing the beneficial effects of physical activity to promote optimal free-living knee joint mechanical loading and improve knee joint health will aid in the development of cost-effective interventions that prevent PTOA and health burden of the disease.
Detailed description
Osteoarthritis (OA) is a leading cause of disability worldwide resulting in severe limitations in daily activities and chronic pain. It is estimated that 35% of posttraumatic OA (PTOA) cases occur after knee injuries and surgeries such as anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR). Optimal free-living mechanical loading, which refers to the forces acting on the knee caused by daily activities, plays an essential role in maintaining knee articular cartilage health. After ACLR, individuals take fewer steps per day as compared to uninjured controls. This results in insufficient free-living mechanical loading to joint tissues and is associated with early PTOA development. Adequate physical activity (PA) is recommended to help reduce risk of PTOA, but it is unclear how changes in PA acutely impact knee joint cartilage health. The overall objective of this pretest-posttest experimental pilot study is to determine how optimizing free-living mechanical loading through PA promotion improves cartilage composition in individuals who demonstrate insufficient free-living mechanical loading after ACLR. PA promotion will be delivered over 8 weeks using commercially available PA monitors and the patients' smartphone to provide daily personalized and achievable step goals to increase daily step counts to a level consistent with healthy PA participation. The hypothesis for aim 1 is that MRI markers of proteoglycan density associated with PTOA development will improve after 8-weeks of PA promotion exposure. Hypothesis for aim 2 is that greater changes in steps per day will be associated with improved proteoglycan density. Change in MRI markers of proteoglycan density and steps per day will be assessed using a pretest-posttest design in 8 adults who are 6 months to 5 years post-ACLR with insufficient mechanical loading (\<8,000 steps per day)24 and suboptimal quality of life (quality of life survey\<87.5). Outcomes will be collected before (pretest) and after (posttest) 8-weeks of PA promotion. For the PA promotion, participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day. The proposed work is innovative, in that this study will use a novel combination of outcomes that will lead to unprecedented insight into the influence of PA promotion in mitigating early PTOA development.
Interventions
BEHAVIORALPhysical Activity Promotion
After enrolling, participants will be outfitted with a Fitbit Charge 2 activity monitor. The monitor will be worn during all waking hours, and compliance will be considered as a day with ≥ 1,000 steps. Participants will complete a 14-day run-in observation period while wearing the Fitbit but no PA promotion will occur. Individuals who are noncompliant during the run in period (\<10 days with \<1,000 steps) will be removed. Participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day.
Sponsors
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Participants will be included if they: * Provide informed consent and sign a HIPPA form prior to any study procedures are performed * Have completed all other formal physical therapy and therapeutic exercise regimens, and will not be engaging in any other formal therapy for their ACLR during the study * Are between the ages of 18 and 35. * Underwent an ACLR no earlier than 6 months and no later than 5 years prior to enrollment. * Demonstrate \< 8,000 steps per day during the screening phase of the study as assessed using the Actigraph GT9X Link monitor. * Demonstrate clinically relevant-knee symptoms, defined as a Knee Injury and Osteoarthritis Outcomes Score (KOOS) quality of life subscale \< 72.2
Exclusion criteria
Participants will be excluded if: * The participant underwent an ACLR revision surgery due to a previous ACL graft injury. * Multiple ligament surgery was indicated at the time of ACLR surgery. * A lower extremity fracture was suffered during the ACL injury. * The participant has been diagnosed with osteoarthritis in either knee * They have a cochlear implant, metal in body, claustrophobia, or history of seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in T1rho Relaxation Times in the Lateral Tibial Condyle | pre-intervention (baseline), post-intervention (~8 weeks) | change in MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention |
| Change in T1rho Relaxation Times in the Medial Femoral Condyle | pre-intervention (baseline), post-intervention (~8 weeks) | Change in MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention |
| Change in T1rho Relaxation Times in the Medial Tibial Condyle | pre-intervention (baseline), post-intervention (~8 weeks) | Change in MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention |
| Change in T1rho Relaxation Times in the Lateral Femoral Condyle | pre-intervention (baseline), post-intervention (~8 weeks) | change in MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention |
| T1rho Relaxation Times in the Lateral Femoral Condyle Post-intervention | post-intervention (~8 weeks) | MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks) |
| T1rho Relaxation Times in the Medial Femoral Condyle at Baseline | pre-intervention (baseline) | MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at pre-intervention (baseline) |
| T1rho Relaxation Times in the Medial Femoral Condyle Post-intervention | post-intervention (~8 weeks) | MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks) |
| T1rho Relaxation Times in the Lateral Femoral Condyle at Baseline | pre-intervention (baseline) | MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e., proteoglycan density) at pre-intervention (baseline) |
| T1rho Relaxation Times in the Medial Tibial Condyle at Baseline | pre-intervention (baseline) | MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline) |
| T1rho Relaxation Times in the Medial Tibial Condyle Post-intervention | post-intervention (~8 weeks) | MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks) |
| T1rho Relaxation Times in the Lateral Tibial Condyle at Baseline | pre-intervention (baseline) | MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline) |
| T1rho Relaxation Times in the Lateral Tibial Condyle Post-intervention | post-intervention (~8 weeks) | MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks) |
| Change in Daily Steps | pre-intervention (baseline), post-intervention (~8 weeks) | Change in average steps per day over 7 day physical activity monitor wear pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale | pre-intervention (baseline) | Knee injury Osteoarthritis Outcome Score (KOOS) Quality of Life subscale to measure knee-related quality of life at pre-intervention (baseline). A higher score indicates better knee-related quality of life. Min = 0 and Max = 100 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days Participant is Compliant With Fitbit Monitor Wear (>1,000 Steps Per Day) | up to post-intervention (~8 weeks) | physical activity promotion intervention compliance |
| Percentage of Patients Retained at Post-intervention Visit (~8 Weeks) Physical Activity Promotion Intervention Retention | post-intervention (~8 weeks) | physical activity promotion intervention retention |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Physical Activity Promotion Group Participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day.
Physical Activity Promotion: After enrolling, participants will be outfitted with a Fitbit Charge 2 activity monitor. The monitor will be worn during all waking hours, and compliance will be considered as a day with ≥ 1,000 steps. Participants will complete a 14-day run-in observation period while wearing the Fitbit but no PA promotion will occur. Individuals who are noncompliant during the run in period (\<10 days with \<1,000 steps) will be removed. Participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of time | 1 |
Baseline characteristics
| Characteristic | Physical Activity Promotion Group |
|---|---|
| Age, Continuous | 25.7 years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 4 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Change in Daily Steps
Change in average steps per day over 7 day physical activity monitor wear pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention
Time frame: pre-intervention (baseline), post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Change in Daily Steps | 2054 steps/day | Standard Deviation 3795 |
Primary
Change in T1rho Relaxation Times in the Lateral Femoral Condyle
change in MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention
Time frame: pre-intervention (baseline), post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Change in T1rho Relaxation Times in the Lateral Femoral Condyle | -0.81 ms | Standard Deviation 1.91 |
95% CI: [-0.88, 0.71]
Primary
Change in T1rho Relaxation Times in the Lateral Tibial Condyle
change in MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention
Time frame: pre-intervention (baseline), post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Change in T1rho Relaxation Times in the Lateral Tibial Condyle | -1.18 ms | Standard Deviation 1.22 |
95% CI: [-0.87, 0.73]
Primary
Change in T1rho Relaxation Times in the Medial Femoral Condyle
Change in MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention
Time frame: pre-intervention (baseline), post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Change in T1rho Relaxation Times in the Medial Femoral Condyle | -0.50 ms | Standard Deviation 3.71 |
95% CI: [-0.67, 0.9]
Primary
Change in T1rho Relaxation Times in the Medial Tibial Condyle
Change in MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention
Time frame: pre-intervention (baseline), post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Change in T1rho Relaxation Times in the Medial Tibial Condyle | -1.11 ms | Standard Deviation 1.31 |
95% CI: [-0.48, 0.94]
Primary
T1rho Relaxation Times in the Lateral Femoral Condyle at Baseline
MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e., proteoglycan density) at pre-intervention (baseline)
Time frame: pre-intervention (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Lateral Femoral Condyle at Baseline | 51.40 ms | Standard Deviation 2.69 |
Primary
T1rho Relaxation Times in the Lateral Femoral Condyle Post-intervention
MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks)
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Lateral Femoral Condyle Post-intervention | 50.60 ms | Standard Deviation 2.48 |
95% CI: [-0.44, 1.24]
Primary
T1rho Relaxation Times in the Lateral Tibial Condyle at Baseline
MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)
Time frame: pre-intervention (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Lateral Tibial Condyle at Baseline | 51.69 ms | Standard Deviation 4.92 |
Primary
T1rho Relaxation Times in the Lateral Tibial Condyle Post-intervention
MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks)
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Lateral Tibial Condyle Post-intervention | 50.51 ms | Standard Deviation 4.36 |
95% CI: [-0.05, 1.93]
Primary
T1rho Relaxation Times in the Medial Femoral Condyle at Baseline
MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)
Time frame: pre-intervention (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Medial Femoral Condyle at Baseline | 53.48 ms | Standard Deviation 4.58 |
Primary
T1rho Relaxation Times in the Medial Femoral Condyle Post-intervention
MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks)
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Medial Femoral Condyle Post-intervention | 52.98 ms | Standard Deviation 3.23 |
95% CI: [-0.68, 0.93]
Primary
T1rho Relaxation Times in the Medial Tibial Condyle at Baseline
MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)
Time frame: pre-intervention (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Medial Tibial Condyle at Baseline | 54.48 ms | Standard Deviation 3.62 |
Primary
T1rho Relaxation Times in the Medial Tibial Condyle Post-intervention
MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at post-intervention (\ 8 weeks)
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | T1rho Relaxation Times in the Medial Tibial Condyle Post-intervention | 53.38 ms | Standard Deviation 3.03 |
95% CI: [-0.13, 1.77]
Secondary
Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale
Knee injury Osteoarthritis Outcome Score (KOOS) Quality of Life subscale to measure knee-related quality of life at pre-intervention (baseline). A higher score indicates better knee-related quality of life. Min = 0 and Max = 100
Time frame: pre-intervention (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale | 63.5 score on a scale | Standard Deviation 22.5 |
Secondary
Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale
Knee injury Osteoarthritis Outcome Score Quality of Life subscale (KOOS) Quality of Life subscale to measure knee-related quality of life at post-intervention. A higher score indicates better knee-related quality of life. Min = 0 and Max = 100
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale | 69.8 score on a scale | Standard Deviation 25.4 |
95% CI: [-1.24, 0.44]
Other Pre-specified
Percentage of Days Participant is Compliant With Fitbit Monitor Wear (>1,000 Steps Per Day)
physical activity promotion intervention compliance
Time frame: up to post-intervention (~8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Promotion Group | Percentage of Days Participant is Compliant With Fitbit Monitor Wear (>1,000 Steps Per Day) | 98.00 percent of days | Standard Deviation 0.02 |
Other Pre-specified
Percentage of Patients Retained at Post-intervention Visit (~8 Weeks) Physical Activity Promotion Intervention Retention
physical activity promotion intervention retention
Time frame: post-intervention (~8 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Physical Activity Promotion Group | Percentage of Patients Retained at Post-intervention Visit (~8 Weeks) Physical Activity Promotion Intervention Retention | 86 percentage of participants |