Hyaluronic Acid vs Platelet Rich Plasma: Effects on Clinical Outcomes and Intra-articular Biology for the Treatment of Knee Osteoarthritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hyaluronic Acid vs Platelet Rich Plasma: Prospective Double-blind Randomized Controlled Trial Comparing Clinical Outcomes and the Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: Platelet-rich Plasma (PRP)
* Biological: Hyaluronic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hyaluronic Acid (HA)<br>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. | Biological: Hyaluronic Acid<br> <br> |
| Experimental: Platelet-rich Plasma (PRP)<br>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. | Biological: Platelet-rich Plasma (PRP)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | 
| 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. | 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. | 
| 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. | This will be assessed as a change from pre-treatment visit to 1 year post treatment. | 
| 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 | Primary outcome will be change from pre-treatment to 6-month post treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet-rich plasma, hyaluronic acid