Synovial Fluid Biomarkers Pre and Post Hymovis Knee Injection

Study Overview
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Brief Summary
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This NJH Investigator Initiated Study funded by Fidia will prospectively perform 2 ultrasound (US) guided knee aspirations in patients with knee osteoarthritis using a pneumatic compressive device (KneeTap ™) at baseline and at 3 months following 2 Hymovis® injections. Synovial fluid catabolic and anabolic proteins will be compared to those values in the peripheral blood and correlated with clinical outcome measurements at 3 ,6 and 12 months compared to baseline values; WOMAC, SF 36, visual analog pain scale, 6 minute walking distance and SF volumes quantitated by US.

Detailed Description
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50 Subjects between 21-80 years with a BMI < 40 with mild to moderate knee osteoarthritis on x ray (KL grade II or III) will have a ultrasound guided arthrocentesis with an external pneumatic compression device (KneeTap) and if > 0.5 ml of synovial fluid is obtained they will received the first of 2 FDA approved Hymovis knee injections. A second ultrasound guided Hymovis intra-synovial space injection will be administered in one week with a repeat arthrocentesis in 3 months. Subjects will be compensated $ 50 for each of 4 of 5 study visits. Clinical outcome measures at study visits 1, 3 (3 months) 4 at (6 months) and 5 (12 months will include: VAS (Visual analog Global pain (1-10), SF -36 ,WOMAC questionnaires (Western Ontario and McMaster University Arthritis Index pain Scale), measured distance on 6 minute walking distance test and synovial fluid depth measured by ultrasound. The Synovial fluid biomarker panel will include values of over 45 separate cytokines,.chemokines and proteins from subjects pre vs post Hymovis injections and compared to values in the peripheral blood obtained simultaneously. SF biomarker analysis will be performed on cryopreserved samples using fluorescence multiplex bead based assays (Luminex) or by ELISA. All values as well as clinical outcome parameters will be entered into the REDCap system for statistical analysis

Official Title
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Alterations in Knee Synovial Fluid Biomarkers and Volume Following Hymovis Injections Using a Pneumatic Assistive Compression Device and Ultrasound Guided Arthrocentesis: Correlation With Clinical Outcomes

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Hymovis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild to moderate knee osteoarthritis on x ray age 21-80 Exclusion Criteria pregnant BMI > 40 history of systemic immune disorders knee arthroplasty with replacement knee infection or surgery within 1 year glucocorticoid injection within 3 months inability to ambulate for 6 minutes without walking assistive devices unable to provide informed consent patients with a clinical contra-indication for an arthrocentesis or adverse reaction to prior intra-articular lidocaine or HA injections.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Hymovis|All subjects will receive 2 ultrasound guided Hymovis injections and the goal of the study is to correlate responsiveness to subjects unique SF biomarker panel results before the first Hymovis injection and identify potential mechanism of action of those OA patients who receive the greatest benefit.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC scores (Western Ontario and McMaster University Osteoarthritis Index) | Self reported numeric values: on pain, stiffness and 17 items of limitations on physical function scored as 0-5 (none, mild, moderate, severe or extreme) | Change from baselinescore values to those over 12 months | 
| SF 36 scores (Quality of Life Questionnaire) | Self reported numeric values based upon multiple domains; assessment of over all health, 0-4, (excellent , very good, good, fair and poor) and score compared to the prior year, 0-4, (much better, somewhat better, about the same, somewhat worse, much worse) and 10 functional daily living activity questions with score 0-2, (not at all limited, limited a little, and limited a lot) and 4 questions on patients health compared to others expectations or worsen or excellent health and if they more easily become sick 0-4, (false, mostly false, don't know, mostly true or definitely true. Higher scores indicate worse health and disability. | Change from baseline score values to those over 12 months | 
| VAS (Visual analogue scale) score for self reported pain | Self Reported patient assessment of pain from 0 I(no pain) on the left to 10 worst pain ever. The paint selects their value on a continuous 10 cm line. A higher numeric number on a 0 -10 scale selected indicates more severe pain. | Change from baseline score values to those over 12 months | 
| 6 minute walking distance | The measured distance in meters walked during a 6 minute supervised walk on level ground. | Change in distance walked from baseline to that distance walked over 12 months | 
| Synovial fluid depth | Ultrasound measurement in millimeters of the maximum SF depth during external pneumatic compression. | Change in the depth of knee synovial fluid from baseline values to those at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Synovial fluid and peripheral blood biomarkers | 54 separate cytokines ,chemokines and proteins which can impact cartilage health will be measured in the synovial fluid by ELISA and Luminex multiplex platforms on cryopreserved samples to determine the levels of these catabolic inflammatory or anabolic proteins which may impact cartilage health. | Change in the baseline levels of biomarkers in pg/ml to the levels 3 months after the first of 2 Hymovis injections |