Investigating Orthobiologics After PRP and Photobiomodulation for Knee Osteoarthritis

Knee Osteoarthritis Clinical Trial

Official title:

Investigating Orthobiologics After Platelet-Rich Plasma and Photobiomodulation Treatment of Knee Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06122116
• Other study ID #: Photomedicine Project 11
• Status: Recruiting
• Phase: N/A
• Start date: October 13, 2023
• Est. completion date: May 10, 2024

Study information

• Verified date: February 2024
• Source: Musculoskeletal Injury Rehabilitation Research for Operational Readiness
• Contact: Scott P Grogan
• Phone: 253-968-2083
• Email: kneephotomed[@]genevausa.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research assesses the effects that Photobiomodulation Therapy (PBMT) has on Intra-articular administered Plasma-Rich Platelet (PRP) injections for Knee Osteoarthritis (KOA) treatment through evaluations of synovial and serum inflammatory and reparative biomarkers.

A comparison of Physical Therapy (PT) vs PT + PRP vs PT + PBMT vs PT + PRP + PBMT for KOA treatment is made. The relationship between self-reported pain and functionality and treatment mechanisms is analyzed along with an analysis of the intersectionality between participant self-reported pain and functionality and medicine markers across treatment groups. These aims seek to inform current treatment practices in treating KOA and returning Active-Duty Service Members to duty readiness.

Description:

Post Traumatic Knee Osteoarthritis (PTOA) is a degenerative joint disease resulting in the loss of cartilage due to wear and tear or by an uncharacteristic force applied to the knee. This disease appears frequently in Active-Duty Service Members and is rising in prominence where over 20,000 Knee Osteoarthritis (KOA) cases were detected over a 10-year period. Current treatments such as physical therapy (PT), braces, oral pain relievers, corticosteroid, and hyaluronic acid injections for KOA only address the quality of life and the symptoms but have not demonstrated a reverse in disease progression. Studies have found that Platelet-Rich Plasma (PRP) has shown to be a promising treatment 6-12 months post procedure and may slow KOA progression.

Photobiomodulation therapy (PBMT) is a non-invasive treatment option shown to reduce pain, increase function, and decrease stiffness with or without therapeutic exercises in KOA patients. In combination, PRP and PBMT may increase the recovery benefits while and potentially reduce KOA progression while seeking therapy. The exact dosage for the optimization of treatment with both PRP and PBMT still needs to be analyzed and understood. Therefore, this study will investigate four treatment arms utilizing PT, PT plus PRP, PT plus PBMT, and PT plus PRP plus PBMT. This discover based and randomized control trial will investigate the effect of PBMT and intra-articular administered PRP treatment on clinical outcomes (e.g., pain scores) and biomolecular signatures (DNA, RNA, or protein levels) in the blood or synovial spaces.The participants' intersectionality between pain, functionality, and precision medicine markers will be analyzed across treatment groups. Follow-up data in the form of questionnaires and activity logs will be collected to monitor study progression.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: May 10, 2024
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• DEERS Eligible

• Between 18-64 (Inclusive)

• Civilian

• Contractor

• Active Duty Service Member

• Knee Osteoarthritis diagnosis

a) at least 3 of the following:

1. >50 years old

2. Morning stiffness < 30 minutes

3. Crepitus on active movements

4. Tenderness of the bony margins of the joint

5. Bony enlargement

6. No palpable warmth

• Fluent in speaking and reading English

• Ability to commit to study intervention and follow-up

• Willing to avoid prohibited treatments while enrolled in the study (NSAIDs/COX-2 inhibitors and ASAs for 5 days prior to and 2 weeks following study injection or beginning of treatment, and oral steroids, steroid injections, and viscos supplementation)

• Radiographic evidence of knee osteoarthritis as assessed by Kellgren-Lawrence grade 1 or higher

Exclusion Criteria:

• Current participation in other research studies for knee OA

• Previous enrollment for contralateral knee

• Hx of arthroscopic surgery on the study knee within the past year

• Hx of arthroplasty on the study knee

• Received dry needling within the past 4 weeks

• Received prolotherapy (e.g. CSI or PRP injection), within past month

• Recent (within the last 3 months) lower extremity injury (e.g., ankle sprain, meniscus tear or sprain, etc.) that required professional medical attention, and occurred in the ipsilateral extremity of the study knee

• Confounding, coexisting pathology suspected to be the primary source of their pain [e.g., acute meniscal tear (with mechanical symptoms), ligamentous changes (with clinical instability) or hemarthrosis]

• Current or chronic sciatica (lumbosacral radiculopathy) resulting in chronic or intermittent lower extremity pain, numbness, or tingling

• Diagnosis of neuropathy affecting sensation to pain

• Diagnosis of inflammatory arthropathy

• Diagnosis of fibromyalgia or chronic fatigue syndrome

• Hx of adverse reaction to PRP injection (either documented in the medical record or shared by the patient during screening)

• Tattoo in treatment area

• Diagnosis of porphyria (light induced allergy) or photosensitive eczema

• Current use of medications associated with sensitivity to heat or light (e.g., amiodarone, chlorpromazine, doxycycline, hydrochlorothiazide, nalidixic acid, naproxen, piroxicam, tetracycline, thioridazine, voriconazole)

• Current use of pacemaker

• Hx of underlying cardiac disease

• Diagnosis of autoimmune disease

• Albinism

• Current pregnancy or plans to become pregnant during intervention period

• Hx of memory problems, dementia, and/or impaired decision-making ability

• Any other serious medical conditions(s) that might preclude optimal outcome and/or interfere with participation (e.g.), intra-articular sepsis, bacteremia, fracture, joint instability, rheumatoid arthritis, osteoporosis, cancer, coagulopathy, etc.)

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Other:
• Physical Therapy
The PT treatment participants receive in this study will be standard of care; that is, the PT treatment regimen will not be standardized across study participants and/or dictated by study-specific criteria. Participants will be referred to the Physical Therapy Department at the Madigan Army Medical Center (MAMC). Number of PT treatments will be documented on a follow-up Chart Review.

Biological:
• Platelet-Rich Plasma Injection
PRP injection procedures will follow current clinical recommendation and standard operating procedures. Prior to the injection, the area will be sterilely prepared and anesthetized with either ethyl chloride spray or lidocaine (limited to the cutaneous and subcutaneous layer, so as not to alter the synovial contents). Then, the participant will receive LP-PRP injection in the affected knee area under ultrasound guidance. Qualified study providers will inject 2-5cc LP-PRP using an 18-gauge 1/5-inch needle for both aspiration and subsequent injection. Study providers will select the injection portal they are most comfortable with, in order to achieve an accurate intra-articular injection. The PRP injection procedure is expected to take approximately one hour.

Device:
• Photobiomodulation Therapy
PBMT is delivered with the LightForce® XPi 25W device through the Smart Hand Piece technology. PBMT will be delivered at 6 J/cm^2 and applied in a circular pattern to the knee area.

Locations

Country	Name	City	State
United States	Madigan Army Medical Center	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Musculoskeletal Injury Rehabilitation Research for Operational Readiness	The Geneva Foundation

Country where clinical trial is conducted

United States, 

References & Publications (26)

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Assis, L, Tim, C, Martignago, C, Rodrigues Gonçalves, S, Muniz Renno, AC. Effectiveness of photobiomodulation therapy and aerobic exercise training on articular cartilage in an experimental model of osteoarthritis in rats. Proceedings of SPIE, Light-Based Diagnosis and Treatment of Infectious Diseases. 2018;10479. https://doi.org/10.1117.12.2291227

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Goncalves AB, Bovo JL, Gomes BS, Pigoso AA, Felonato M, Esquisatto MAM, Filho GJL, do Bomfim FRC. Photobiomodulation (lambda=808nm) and Platelet-Rich Plasma (PRP) for the Treatment of Acute Rheumatoid Arthritis in Wistar Rats. J Lasers Med Sci. 2021 Oct 18;12:e60. doi: 10.34172/jlms.2021.60. eCollection 2021. — View Citation

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Hsu H, Siwiec RM. Knee Osteoarthritis. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507884/ — View Citation

Huang G, Hua S, Yang T, Ma J, Yu W, Chen X. Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors. Exp Ther Med. 2018 Mar;15(3):3096-3102. doi: 10.3892/etm.2018.5794. Epub 2018 Jan 24. — View Citation

Ip D. Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement? Lasers Med Sci. 2015 Dec;30(9):2335-9. doi: 10.1007/s10103-015-1814-6. Epub 2015 Sep 29. — View Citation

Migliorini F, Driessen A, Quack V, Sippel N, Cooper B, Mansy YE, Tingart M, Eschweiler J. Comparison between intra-articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: a Bayesian network meta-analysis. Arch Orthop Trauma Surg. 2021 Sep;141(9):1473-1490. doi: 10.1007/s00402-020-03551-y. Epub 2020 Jul 28. — View Citation

Molloy JM, Pendergrass TL, Lee IE, Chervak MC, Hauret KG, Rhon DI. Musculoskeletal Injuries and United States Army Readiness Part I: Overview of Injuries and their Strategic Impact. Mil Med. 2020 Sep 18;185(9-10):e1461-e1471. doi: 10.1093/milmed/usaa027. — View Citation

Ng NT, Heesch KC, Brown WJ. Strategies for managing osteoarthritis. Int J Behav Med. 2012 Sep;19(3):298-307. doi: 10.1007/s12529-011-9168-3. — View Citation

O'Connell B, Wragg NM, Wilson SL. The use of PRP injections in the management of knee osteoarthritis. Cell Tissue Res. 2019 May;376(2):143-152. doi: 10.1007/s00441-019-02996-x. Epub 2019 Feb 13. — View Citation

Paolillo FR, Paolillo AR, Joao JP, Frasca D, Duchene M, Joao HA, Bagnato VS. Ultrasound plus low-level laser therapy for knee osteoarthritis rehabilitation: a randomized, placebo-controlled trial. Rheumatol Int. 2018 May;38(5):785-793. doi: 10.1007/s00296-018-4000-x. Epub 2018 Feb 26. — View Citation

Peplow PV, Chung TY, Ryan B, Baxter GD. Laser photobiomodulation of gene expression and release of growth factors and cytokines from cells in culture: a review of human and animal studies. Photomed Laser Surg. 2011 May;29(5):285-304. doi: 10.1089/pho.2010.2846. Epub 2011 Feb 10. — View Citation

Rayegani SM, Raeissadat SA, Heidari S, Moradi-Joo M. Safety and Effectiveness of Low-Level Laser Therapy in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. J Lasers Med Sci. 2017 Summer;8(Suppl 1):S12-S19. doi: 10.15171/jlms.2017.s3. Epub 2017 Aug 29. — View Citation

Showery JE, Kusnezov NA, Dunn JC, Bader JO, Belmont PJ Jr, Waterman BR. The Rising Incidence of Degenerative and Posttraumatic Osteoarthritis of the Knee in the United States Military. J Arthroplasty. 2016 Oct;31(10):2108-14. doi: 10.1016/j.arth.2016.03.026. Epub 2016 Mar 21. — View Citation

Stausholm MB, Naterstad IF, Joensen J, Lopes-Martins RAB, Saebo H, Lund H, Fersum KV, Bjordal JM. Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials. BMJ Open. 2019 Oct 28;9(10):e031142. doi: 10.1136/bmjopen-2019-031142. — View Citation

Tomazoni SS, Leal-Junior EC, Frigo L, Pallotta RC, Teixeira S, de Almeida P, Bjordal JM, Lopes-Martins RA. Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain. J Biomed Opt. 2016 Oct 1;21(10):108001. doi: 10.1117/1.JBO.21.10.108001. — View Citation

Tomazoni SS, Leal-Junior EC, Pallotta RC, Teixeira S, de Almeida P, Lopes-Martins RA. Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis. Lasers Med Sci. 2017 Jan;32(1):101-108. doi: 10.1007/s10103-016-2091-8. Epub 2016 Oct 10. — View Citation

Vassao PG, Parisi J, Penha TFC, Balao AB, Renno ACM, Avila MA. Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials. Lasers Med Sci. 2021 Sep;36(7):1341-1353. doi: 10.1007/s10103-020-03223-8. Epub 2021 Jan 3. — View Citation

Xiang A, Deng H, Cheng K, Liu H, Lin L, Qu X, Liu S, Shen X. Laser photobiomodulation for cartilage defect in animal models of knee osteoarthritis: a systematic review and meta-analysis. Lasers Med Sci. 2020 Jun;35(4):789-796. doi: 10.1007/s10103-019-02937-8. Epub 2019 Dec 17. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kellgren Lawrence Classification System (KL)	Kellgren Lawrence Classification System (KL) will score the radiographic evidence of the participant's knee osteoarthritis.; Minimum Score: Grade 0 (none): definite absence of X-ray changes of knee OA; Maximum Score: Grade 4 (severe): Large osteophyte formation, joint space narrowing, definite bone end deformity; Higher grades indicate a worse outcome.	Baseline
Primary	Defense and Veterans Pain Rating Scale (DVPRS)	Defense and Veterans Pain Rating Scale (DVPRS) will capture current pain severity.; Minimum Score: 0 (no pain); Maximum Score: 10 (As bad as it could be, nothing else matters); A higher score indicates, increasing pain.	Baseline
Primary	Defense and Veterans Pain Rating Scale (DVPRS)	Defense and Veterans Pain Rating Scale (DVPRS) will capture current pain severity.; Minimum Score: 0 (no pain); Maximum Score: 10 (As bad as it could be, nothing else matters); A higher score indicates, increasing pain.	Daily, for 6 weeks
Primary	Single Assessment Numeric Evaluation (SANE)	Single Assessment Numeric Evaluation (SANE) will rate the participant's knee osteoarthritis condition as a percentage from normal.; Minimum Score: 0% (Abnormal); Maximum Score: 100% (Fully Normal); An increasing percentage means the closer the participant feels their knee is back to normal function.	Baseline
Primary	Single Assessment Numeric Evaluation (SANE)	Single Assessment Numeric Evaluation (SANE) will rate the participant's knee osteoarthritis condition as a percentage from normal.; Minimum Score: 0% (Abnormal); Maximum Score: 100% (Fully Normal); An increasing percentage means the closer the participant feels their knee is back to normal function.	Daily, for 6 weeks
Primary	Knee Injury Osteoarthritis Outcome Score (KOOS)	Knee Injury Osteoarthritis Outcome Score (KOOS) will ask the participants questions while thinking about their injured knee symptoms in the past week.; Minimum Score: None; Maximum Score: Extreme; On a per question basis, the participant states how significant their knee symptoms are.	Baseline
Primary	Knee Injury Osteoarthritis Outcome Score (KOOS)	Knee Injury Osteoarthritis Outcome Score (KOOS) will ask the participants questions while thinking about their injured knee symptoms in the past week.; Minimum Score: None; Maximum Score: Extreme; On a per question basis, the participant states how significant their knee symptoms are.	3-week follow-up
Primary	Knee Injury Osteoarthritis Outcome Score (KOOS)	Knee Injury Osteoarthritis Outcome Score (KOOS) will ask the participants questions while thinking about their injured knee symptoms in the past week.; Minimum Score: None; Maximum Score: Extreme; On a per question basis, the participant states how significant their knee symptoms are.	6-week follow-up
Primary	The Veterans Rand 12 Item Health Survey (VR-12)	The Veterans Rand 12 Item Health Survey (VR-12) asks participants about their feelings and how well they can do their usual activities.; Minimum Score 1: Poor Maximum Score 1: Excellent Refers to a participant's general health.; Minimum Score 2: Yes, limited a lot Maximum Score 2: No, not limited at all Refers to activity, how their health has limited them.; Minimum Score 3: No, none of the time Maximum Score 3: Yes, all of the time How Physical health has that impacted accomplishments and the kind of work of other activities.; Minimum Score 4: Not at all Maximum Score 4: Extremely Refers to how pain interferes with normal work.; Minimum Score 5: All of the time Maximum Score 5: None of the time Refers to feeling calm, having energy, and whether they feel downhearted.; Minimum Score 6: Much worse Maximum Score 6: Much better A comparison of physical health compared to a year ago and a comparison of emotional health compared to a year ago.	Baseline
Primary	The Veterans Rand 12 Item Health Survey (VR-12)	The Veterans Rand 12 Item Health Survey (VR-12) will ask participants about how they feel and how well they are able to do their usual activities.; Minimum Score 1: Poor Maximum Score 1: Excellent Refers to a participant's general health.; Minimum Score 2: Yes, limited a lot Maximum Score 2: No, not limited at all Refers to activity, how their health has limited them.; Minimum Score 3: No, none of the time Maximum Score 3: Yes, all of the time How Physical health has that impacted accomplishments and the kind of work of other activities.; Minimum Score 4: Not at all Maximum Score 4: Extremely Refers to how pain interferes with normal work.; Minimum Score 5: All of the time Maximum Score 5: None of the time Refers to feeling calm, having energy, and whether they feel downhearted.; Minimum Score 6: Much worse Maximum Score 6: Much better A comparison of physical health compared to a year ago and a comparison of emotional health compared to a year ago.	3-week follow-up
Primary	The Veterans Rand 12 Item Health Survey (VR-12)	The Veterans Rand 12 Item Health Survey (VR-12) will ask participants about how they feel and how well they are able to do their usual activities.; Minimum Score 1: Poor Maximum Score 1: Excellent Refers to a participant's general health.; Minimum Score 2: Yes, limited a lot Maximum Score 2: No, not limited at all Refers to activity, how their health has limited them.; Minimum Score 3: No, none of the time Maximum Score 3: Yes, all of the time How Physical health has that impacted accomplishments and the kind of work of other activities.; Minimum Score 4: Not at all Maximum Score 4: Extremely Refers to how pain interferes with normal work.; Minimum Score 5: All of the time Maximum Score 5: None of the time Refers to feeling calm, having energy, and whether they feel downhearted.; Minimum Score 6: Much worse Maximum Score 6: Much better A comparison of physical health compared to a year ago and a comparison of emotional health compared to a year ago.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest ADAMTS-4 &5	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 &5.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest MMP 7 & 9	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7 & 9.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest TGF-B	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: TGF-B.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest Aggrecan	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest HYAL2	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest CRP	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest HA	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest CD14	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest CD16	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest CD64	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest CD64	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest CD16	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest CD14	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest HA	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest CRP	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest HYAL2	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest Aggrecan	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest TGF-B	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest MMP 7 & 9	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7& 9.	Baseline
Primary	Knee Joint Aspiration for Biomarkers of Interest ADAMTS-4 & 5	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 & 5.	Baseline
Primary	Biorepository Blood Draw for Biomarkers of Interest CD64.	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest CD16	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest CD14	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest HA	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest CRP	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest HYAL2	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest Aggrecan	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest TGF-B	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: TGF-B.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest MMP 7 & 9	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7 & 9.	6-week follow-up
Primary	Biorepository Blood Draw for Biomarkers of Interest ADAMTS-4 & 5	4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 & 5.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest ADAMTS-4 & 5	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 & 5.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest MMP 7 & 9	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7 & 9.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest TGF-B	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: TGF-B.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest Aggrecan	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest HYAL2	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest CRP	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest HA	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest CD14	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest CD16	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16.	6-week follow-up
Primary	Knee Joint Aspiration for Biomarkers of Interest CD64	Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64.	6-week follow-up
Primary	Complete Blood Count (CBC) Analysis WBC	Whole blood and PRP spin analysis will be completed to analyze total blood content of WBC.	Baseline
Primary	Complete Blood Count (CBC) Analysis RBC	Whole blood and PRP spin analysis will be completed to analyze total blood content of RBC.	Baseline
Primary	Complete Blood Count (CBC) Analysis HGB	Whole blood and PRP spin analysis will be completed to analyze total blood content of HGB.	Baseline
Primary	Complete Blood Count (CBC) Analysis HCT	Whole blood and PRP spin analysis will be completed to analyze total blood content of HCT.	Baseline
Primary	Complete Blood Count (CBC) Analysis PLT	Whole blood and PRP spin analysis will be completed to analyze total blood content of PLT.	Baseline
Primary	Complete Blood Count (CBC) Analysis LYM%	Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM%.	Baseline
Primary	Complete Blood Count (CBC) Analysis LYM#	Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM#.	Baseline
Primary	Complete Blood Count (CBC) Analysis MON%	Whole blood and PRP spin analysis will be completed to analyze total blood content of MON%.	Baseline
Primary	Complete Blood Count (CBC) Analysis GRA%	Whole blood and PRP spin analysis will be completed to analyze total blood content of GRA%.	Baseline
Primary	Complete Blood Count (CBC) Analysis Neutrophil%	Whole blood and PRP spin analysis will be completed to analyze total blood content of Neutrophil%.	Baseline
Primary	Complete Blood Count (CBC) Analysis Eosinophil%,	Whole blood and PRP spin analysis will be completed to analyze total blood content of Eosinophil%.	Baseline
Primary	Complete Blood Count (CBC) Analysis Basophil%	Whole blood and PRP spin analysis will be completed to analyze total blood content of Basophil%.	Baseline
Primary	Complete Blood Count (CBC) Analysis MON#	Whole blood and PRP spin analysis will be completed to analyze total blood content of MON#.	Baseline