Osteoarthritis
Conditions
Brief summary
This study aims to develop, evaluate and translate highly accelerated imaging sequences (each protocol under 5 minutes) for in-vivo knee Osteoarthritis applications on a standard clinical 3T scanner using novel compression sensing and parallel imaging strategies.The overarching objective of the study is to establish a non-invasive imaging biomarker based on the development of rapid relaxation mapping with compressed sensing (CS) that will be clinically useful for assessment of early Osteoarthritis. A total of 90 subjects including 30 patients with high risk of developing knee osteoarthritis (OA), 30 patients with mild OA and 30 healthy controls will be accrued.
Detailed description
Current noninvasive imaging methods to evaluate knee joints include plain radiographs, computed tomography (CT), and clinical morphological magnetic resonance imaging (MRI) of joint structures. These techniques can only detect later-stage, macroscopic joint structural abnormalities that are irreversible and not amenable to early therapy. This study aims to develop highly accelerated imaging sequences for ex-vivo knee OA applications on a standard clinical 3T scanner using novel CS and parallel imaging (PI) strategies.
Interventions
DEVICEPRISMA 3T MRI scanner (Siemens Medical Solutions)
A baseline MRI exam consisting of accelerated 3D-T1p, and T2, MRI will be performed. Longitudinal follow-up MRI exams (24 months) will be repeated on the same knee on all OA patients.
Sponsors
National Institutes of Health (NIH)
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients in the HJD OA database, ages 40-75 with high risk of developing OA as defined by: (i) KL score of 0 (ii) Knee pain present in at least 1 knee (iii) Normal radiographs, (iv) At least one abnormal clinical MR finding such as prior knee injury, overweight or traumatic bone marrow edema lesions * Patients ages 40-75 with early OA as determined by KL scores 1-2 * Healthy controls in the HJD OA database (KL score 0, no knee pain, no meniscal or ligament tears)
Exclusion criteria
* Contraindications for MRIs (e.g. pacemakers, ferromagnetic vascular clips, metal implants, claustrophobia, etc). * Subjects with any joint disease (example: Rheumatoid or inflammatory arthritis) other than knee OA, corticosteroid injections within the previous 3 months, and history of avascular necrosis, Paget's disease of bone, Wilson's disease, gout, total knee replacement (or plan for replacement within next 24 months). * Major co-morbidities such as diabetes, mellitus, cancer, congestive heart failure and chronic infectious diseases. * Alignment interventions such as insoles and knee braces * Vulnerable patients will not be recruited for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in T1ρ Relaxation Time | Baseline, Month 24 | MRI exam of accelerated 3D-T1p conducted on whole knee joint specimens to determine cartilage composition, measured as T1ρ relaxation time. T1ρ MRI relaxation times refer to the proteoglycan density within cartilage. Images taken at baseline and at Month 24. |
| Change From Baseline in T2 Relaxation Time | Baseline, Month 24 | MRI exam of accelerated T2 conducted on whole knee joint specimens to determine cartilage composition, measured as T2 relaxation time. T2 relaxation represents the time constant of the molecular motion of water in cartilage, which is influenced by the composition of collagen and specifically reflects changes to the extracellular matrix. Images taken at baseline and at Month 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster University OA Index (WOMAC) Score | Baseline, Month 24 | The WOMAC is a 33-item self assessment of how participants feel about their knee and how well they can perform usual activities. The questionnaire contains 4 separately scored subscales - Symptoms; Stiffness; Pain and Function; and Daily Living. The total score is a percentage score from 0 to 100; lower scores represent less pain, less stiffness, and better physical function; higher scores indicate greater pain, greater stiffness, and worse physical function. A decrease in scores indicates participants' health improved during the observational period. |
| Change From Baseline in Knee Injury and OA Outcomes Score (KOOS) | Baseline, Month 24 | Knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales - Pain; Other Symptoms; Function in daily living (ADL); Function in Sport and Recreation (Sport/Rec); and knee-related Quality of Life (QOL). The total score is a percentage score from 0 to 100; 0 represents extreme problems and 100 represents no problems. An increase in scores indicates participants' health improved during the observational period. |
| Change From Baseline in Physical Activity Scale for the Elderly (PASE) Scores | Baseline, 24 Months | Self-assessment of multiple domains of activity in older adults. Questions evaluate both occupational and non-occupational knee bending, squatting and stair climbing. Total scores range from 0 to 400 or above and are quantified based on frequency values and weights for these activities. Higher scores indicate higher levels of physical activity. An increase in scores indicates physical activity increased during the observational period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Risk for Osteoarthritis High risk of developing knee OA has been defined by having knee pain but normal radiographs (Kellgren-Lawrence score 0 i.e. KL0) on both knees but at least one abnormal finding on clinical MR protocol such as overweight, prior knee injury (ligaments or menisci) or traumatic bone marrow edema lesions.
PRISMA 3T MRI scanner (Siemens Medical Solutions): A baseline MRI exam consisting of accelerated 3D-T1p, and T2, MRI will be performed. Longitudinal follow-up MRI exams (24 months) will be repeated on the same knee on all OA patients. | 6 |
| Mild Osteoarthritis PRISMA 3T MRI scanner (Siemens Medical Solutions): A baseline MRI exam consisting of accelerated 3D-T1p, and T2, MRI will be performed. Longitudinal follow-up MRI exams (24 months) will be repeated on the same knee on all OA patients. | 3 |
| Healthy Controls Controls will be age/gender matched to patients within 2 years of age.
PRISMA 3T MRI scanner (Siemens Medical Solutions): A baseline MRI exam consisting of accelerated 3D-T1p, and T2, MRI will be performed. | 30 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 4 | 0 |
Baseline characteristics
| Characteristic | High Risk for Osteoarthritis | Total | Healthy Controls | Mild Osteoarthritis |
|---|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 4.5 | 59.1 years STANDARD_DEVIATION 8.2 | 57.9 years STANDARD_DEVIATION 8.6 | 64.7 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 26 Participants | 20 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 9 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 12 Participants | 11 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 9 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 16 Participants | 11 Participants | 1 Participants |
| Region of Enrollment United States | 6 participants | 39 participants | 30 participants | 3 participants |
| Sex: Female, Male Female | 4 Participants | 21 Participants | 15 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 18 Participants | 15 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 30 |
| other Total, other adverse events | 0 / 6 | 0 / 3 | 0 / 30 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 30 |
Outcome results
Primary
Change From Baseline in T1ρ Relaxation Time
MRI exam of accelerated 3D-T1p conducted on whole knee joint specimens to determine cartilage composition, measured as T1ρ relaxation time. T1ρ MRI relaxation times refer to the proteoglycan density within cartilage. Images taken at baseline and at Month 24.
Time frame: Baseline, Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk for Osteoarthritis | Change From Baseline in T1ρ Relaxation Time | 2.1 milliseconds | Standard Deviation 2.2 |
| Mild Osteoarthritis | Change From Baseline in T1ρ Relaxation Time | 13.3 milliseconds | Standard Deviation 9.4 |
Primary
Change From Baseline in T2 Relaxation Time
MRI exam of accelerated T2 conducted on whole knee joint specimens to determine cartilage composition, measured as T2 relaxation time. T2 relaxation represents the time constant of the molecular motion of water in cartilage, which is influenced by the composition of collagen and specifically reflects changes to the extracellular matrix. Images taken at baseline and at Month 24.
Time frame: Baseline, Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk for Osteoarthritis | Change From Baseline in T2 Relaxation Time | 0.7 milliseconds | Standard Deviation 6.3 |
| Mild Osteoarthritis | Change From Baseline in T2 Relaxation Time | 11 milliseconds | Standard Deviation 7.8 |
Secondary
Change From Baseline in Knee Injury and OA Outcomes Score (KOOS)
Knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales - Pain; Other Symptoms; Function in daily living (ADL); Function in Sport and Recreation (Sport/Rec); and knee-related Quality of Life (QOL). The total score is a percentage score from 0 to 100; 0 represents extreme problems and 100 represents no problems. An increase in scores indicates participants' health improved during the observational period.
Time frame: Baseline, Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk for Osteoarthritis | Change From Baseline in Knee Injury and OA Outcomes Score (KOOS) | 6 score on a scale | Standard Deviation 11.9 |
| Mild Osteoarthritis | Change From Baseline in Knee Injury and OA Outcomes Score (KOOS) | 6.2 score on a scale | Standard Deviation 4.5 |
Secondary
Change From Baseline in Physical Activity Scale for the Elderly (PASE) Scores
Self-assessment of multiple domains of activity in older adults. Questions evaluate both occupational and non-occupational knee bending, squatting and stair climbing. Total scores range from 0 to 400 or above and are quantified based on frequency values and weights for these activities. Higher scores indicate higher levels of physical activity. An increase in scores indicates physical activity increased during the observational period.
Time frame: Baseline, 24 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk for Osteoarthritis | Change From Baseline in Physical Activity Scale for the Elderly (PASE) Scores | 3.8 score on a scale | Standard Deviation 10.1 |
| Mild Osteoarthritis | Change From Baseline in Physical Activity Scale for the Elderly (PASE) Scores | 3.2 score on a scale | Standard Deviation 4.5 |
Secondary
Change From Baseline in Western Ontario and McMaster University OA Index (WOMAC) Score
The WOMAC is a 33-item self assessment of how participants feel about their knee and how well they can perform usual activities. The questionnaire contains 4 separately scored subscales - Symptoms; Stiffness; Pain and Function; and Daily Living. The total score is a percentage score from 0 to 100; lower scores represent less pain, less stiffness, and better physical function; higher scores indicate greater pain, greater stiffness, and worse physical function. A decrease in scores indicates participants' health improved during the observational period.
Time frame: Baseline, Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk for Osteoarthritis | Change From Baseline in Western Ontario and McMaster University OA Index (WOMAC) Score | 5.4 score on a scale | Standard Deviation 8.6 |
| Mild Osteoarthritis | Change From Baseline in Western Ontario and McMaster University OA Index (WOMAC) Score | 2.5 score on a scale | Standard Deviation 4.1 |