Osteoarthritis, Knee
Conditions
Keywords
platelet-rich plasma, hyaluronic acid
Brief summary
In this, prospective, double-blind study, patients with mild to moderate symptomatic knee osteoarthritis will be randomized to receive either a series of leukocyte poor, platelet-rich plasma or hyaluronic acid injections under ultrasound guidance. Clinical data in the form of subjective outcome measures will be collected pre-treatment and at four time intervals across a 1-year period. Synovial fluid will also collected for analysis of pro- and anti-inflammatory markers pre-treatment, and at 12 and 24 weeks.
Detailed description
The objective of this double-blind prospective randomized clinical trial is to compare the effects of PRP to HA in patients with mild to moderate OA using biologic and clinical correlates of outcomes associated with the treatment of OA. The investigators will test the null hypothesis that there are no differences in clinical outcomes as measured by validated clinical scoring systems for OA, nor is there any difference in intra-articular biology between groups of patients treated with HA and those treated with PRP over time. This study was a prospective, randomized, double blind, comparative clinical trial with an allocation ratio of 1:1 that underwent IRB approval at the principal institution. Between 2011 and 2014 patients will be screened for participation. All comers with a diagnosis of osteoarthritis of the knee between 18 and 80 years of age will be screened. Treatment and Evaluation Patients who meet inclusion criteria will be randomized via an electronic randomization process into two groups: one receiving intra-articular PRP and the other, intra-articular HA. Non-clinical staff will perform randomization, clinical staff performed the injections, and results and analyses will be performed by the primary research team. Patients and the primary research team performing analysis will be blinded to assignments. All patients will undergo a 10 ml blood draw for PRP preparation and a 3 ml peripheral blood draw for a complete blood count with leukocyte differential. This will be performed on patients who received HA to maintain patient blinding and to characterize the peripheral white blood cells (WBC) and platelet counts. A complete blood count (CBC) will be completed on PRP prior to injection to evaluate the fold increase in platelet concentration and to confirm rarity of red white blood cells. A synovial fluid aspirate of approximately 2cc will be performed under ultrasound guidance just prior to each PRP or HA injection for ELISA analysis of basal and post-treatment intra-articular environment. After treatment, patients will be instructed to limit the use of the leg for at least 24 hours and use cold therapy/icing for discomfort. During this treatment period rest or mild exertion activities (such as exercise bike, aquatic therapy) are recommended, followed by gradual return to sports or recreational activities as tolerated.
Interventions
BIOLOGICALPlatelet-rich Plasma (PRP)
BIOLOGICALHyaluronic Acid
Sponsors
Cornell University
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-80 years old * Mild to moderate unilateral, symptomatic osteoarthritis of the knee * No recent (within 3 months) intra-articular intervention to the affected knee
Exclusion criteria
* Knee instability * Varus/Valgus alignment \>5 degrees * Bilateral knee osteoarthritis * Systemic inflammatory arthropathy * Known history of anemia, coagulopathy, or present use of blood thinners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International Knee Documentation Committee Score (IKDC | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | This is a scale from 1-100, 100 being the worst pain imaginable and 1 being no pain at all that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment. |
| Western Ontario and McMaster Universities Arthritis Index | This will be assessed as a change from pre-treatment visit to 1 year post treatment. 6-weeks post-treatment, 6-months post treatment, and finally at 1-year post treatment will be documented for the purpose of trending data. | This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment. |
| Lysholm Knee Score | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment. |
| Biologic Testing of Synovial Fluid Via ELISA Assays | Primary outcome will be change from pre-treatment to 6-month post treatment. | ELISA analysis will be performed for the following biological markers: IL-1β, IL-1ra, IL-6, IL-8, TNFα |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hyaluronic Acid (HA) Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection.
Hyaluronic Acid | 59 |
| Platelet-rich Plasma (PRP) Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume.
Platelet-rich Plasma (PRP) | 52 |
| Total | 111 |
Baseline characteristics
| Characteristic | Hyaluronic Acid (HA) | Platelet-rich Plasma (PRP) | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 10.5 | 55.9 years STANDARD_DEVIATION 10.4 | 56.3 years STANDARD_DEVIATION 10.4 |
| BMI | 29 kg/m^2 STANDARD_DEVIATION 6.4 | 27.4 kg/m^2 STANDARD_DEVIATION 3.9 | 28.2 kg/m^2 STANDARD_DEVIATION 5.1 |
| Sex: Female, Male Female | 30 Participants | 21 Participants | 51 Participants |
| Sex: Female, Male Male | 20 Participants | 28 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 59 | 0 / 52 |
| serious Total, serious adverse events | 0 / 59 | 0 / 52 |
Outcome results
Primary
International Knee Documentation Committee Score (IKDC
This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time frame: This will be assessed as a change from pre-treatment visit to 1 year post treatment.
Population: 9 HA patients and 3 PRP from the original cohort were lost to follow up which is why 50 HA and 49 PRP patients were included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronic Acid (HA) | International Knee Documentation Committee Score (IKDC | 65.5 units on a scale | Standard Error 3.6 |
| Platelet-rich Plasma (PRP) | International Knee Documentation Committee Score (IKDC | 55.8 units on a scale | Standard Error 3.8 |
Secondary
Biologic Testing of Synovial Fluid Via ELISA Assays
ELISA analysis will be performed for the following biological markers: IL-1β, IL-1ra, IL-6, IL-8, TNFα
Time frame: Primary outcome will be change from pre-treatment to 6-month post treatment.
Population: IL-1B
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronic Acid (HA) | Biologic Testing of Synovial Fluid Via ELISA Assays | 0.14 units on a scale | Standard Error 0.005 |
| Platelet-rich Plasma (PRP) | Biologic Testing of Synovial Fluid Via ELISA Assays | 0.34 units on a scale | Standard Error 0.16 |
Secondary
Lysholm Knee Score
This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time frame: This will be assessed as a change from pre-treatment visit to 1 year post treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronic Acid (HA) | Lysholm Knee Score | 55.8 units on a scale | Standard Error 3.8 |
| Platelet-rich Plasma (PRP) | Lysholm Knee Score | 65.5 units on a scale | Standard Error 3.6 |
Secondary
Visual Analogue Scale (VAS)
This is a scale from 1-100, 100 being the worst pain imaginable and 1 being no pain at all that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time frame: This will be assessed as a change from pre-treatment visit to 1 year post treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronic Acid (HA) | Visual Analogue Scale (VAS) | 57.3 units on a scale | Standard Error 3.8 |
| Platelet-rich Plasma (PRP) | Visual Analogue Scale (VAS) | 44 units on a scale | Standard Error 4.6 |
Secondary
Western Ontario and McMaster Universities Arthritis Index
This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time frame: This will be assessed as a change from pre-treatment visit to 1 year post treatment. 6-weeks post-treatment, 6-months post treatment, and finally at 1-year post treatment will be documented for the purpose of trending data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronic Acid (HA) | Western Ontario and McMaster Universities Arthritis Index | 4 units on a scale | Standard Error 0.6 |
| Platelet-rich Plasma (PRP) | Western Ontario and McMaster Universities Arthritis Index | 3.02 units on a scale | Standard Error 0.48 |