Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints

NCT01613833 | Suspended

• 1 other identifier: Scu.Cyt.003
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Osteoarthritis (OA) is the irreversible degeneration of articular cartilage and underlying bone. It poses a major healthcare problem as it is the leading cause of joint disease and disability in the United States. It was traditionally thought that OA was a consequence of aging and joint trauma. However, it is now thought that OA is a result of the interplay of multiple genetic, biomechanical, and biochemical factors that disrupt the normal homeostasis of cartilage, bone, and synovium. OA is classified into two groups, primary and secondary. Primary OA is classically polyarticular and peripheral while secondary OA can commonly be attributed to a specific cause, limited to a singular joint, and a result of trauma. It is known as post-traumatic OA (PTOA). Other causes of secondary OA include congenital disorders, calcium pyrophosphate dehydrate deposition disease, and other diseases. Regardless of classification, genetic variation in the normal metabolism of cartilage and bone is thought to play a role in the progression of OA. Furthermore, the polyarticular presentation of primary idiopathic osteoarthritis suggests that it may have a stronger genetic component as compared to secondary OA, indicating a deviation from normal cartilage and bone homeostasis. Matrix metalloproteinases (MMP) and their inhibitors take part in the metabolism of cartilage and bone. MMPs are enzymes that catalyze the degradation of elements within joint spaces while their inhibitors cease this activity. Alpha-2-Macroglobulin (A2M) is a naturally-occurring plasma glycoprotein that functions throughout multiple tissues and extracellular spaces as a protease inhibitor but does not normally reach high levels within the intra-articular joint space. A2M is believed to modulate the systemic inflammatory response by its ability to bait, trap, and clear various MMPs and cytokines. Concentrated A2M directly addresses the roles of cytokines and catabolic enzymes known to participate in the development of osteoarthritis. Cytonics has shown that A2M can inhibit cartilage degradation in vitro. As the role of MMPs and protease inhibitors have emerged as key components of OA, the investigation of regulators of MMP has become of interest to elucidate the pathogenesis and possible novel treatments of OA. This study aims to measure and correlate the levels of alpha-2-Macroglobulin (A2M) in plasma and knee joint OA between primary post-traumatic (PTOA) and secondary osteoarthritis groups.

Conditions

Osteoarthritis of the Knee

Keywords

Alpha2 macroglobulin; Osteoarthritis; plasma and synovium

Outcome Measures

Primary Outcomes (1)

• A2M levels in plasma and synovium

  A2M levels will be drawn from plasma and synovium on the date of surgery for total knee arthroplasty. samples will then be stored properly and analyzed once data collection is complete.

  Analyzed at the end of data collection within; approximately within 3 months of collection

Study Arms (2)

Primary OA Group

Subjects who are to undergo primary total knee arthroplasty due to primary OA which may include but is not limited to bilateral or peripheral involvement with no significant history of overuse or trauma to the joint.

Procedure: Blood Draw; Procedure: Joint Aspirate Harvest

Secondary/Post-traumatic OA Group

Subjects who are to undergo primary total knee arthroplasty due to osteoarthritis of the knee that is secondary to injury or overuse of the joint.

Procedure: Blood Draw; Procedure: Joint Aspirate Harvest

Interventions

Blood Draw PROCEDURE

Blood drawn for A2M levels to be assayed at Cytonics

Also known as: Phlebotomy

Primary OA Group

Joint Aspirate Harvest PROCEDURE

Joint aspirate harvested for A2M levels to be assayed at Cytonics

Also known as: Synoviual Fluid

Primary OA Group

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing total knee arthroplasty

You may qualify if:

• Group 1, Non-traumatic primary OA:
• Subject scheduled to undergo primary unilateral total knee arthroplasty for primary osteoarthritis as determined by an orthopedic surgeon
• Subject is male or female over 45-75 years of age
• Subject is able to read and understand informed consent form and must subsequently sign and date consent form
• Group 2, Secondary post-traumatic/overuse OA:
• Subject scheduled to undergo unilateral total knee arthroplasty secondary osteoarthritis as determined by an orthopedic surgeon, which MUST include either previous injury or surgery to the operative knee.
• Subject is male or female 45-75 years of age
• Subject is able to read and understand informed consent form and must subsequently sign and date consent form

You may not qualify if:

• Group 1, Non-traumatic primary OA:
• History of inflammatory arthritis (e.g. rheumatoid arthritis, ankylosing spondylitis)
• Indication for surgery other than osteoarthritis
• Revision total knee arthroplasty
• Age \>75, age \<44
• Unable to read, understand, or sign informed consent form
• Previous knee infection
• Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease
• Group 2, Secondary post-traumatic/overuse OA:
• History of inflammatory arthritis (e.g. rheumatoid arthritis, ankyolosing spondylitis)
• Indication for surgery other than osteoarthritis
• Age \>75, age \<44
• Unable to read, understand, or sign informed consent form
• Previous knee infection
• Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease

Sponsors & Collaborators

• Scuderi, Gaetano J., M.D.: lead

Study Sites (1)

Stanford University Hospital

Palo Alto, California, 94304, United States

Location

Related Publications (8)

• Creamer P, Hochberg MC. Osteoarthritis. Lancet. 1997 Aug 16;350(9076):503-8. doi: 10.1016/S0140-6736(97)07226-7. No abstract available.

  PMID: 9274595 BACKGROUND

• Heliovaara M, Makela M, Impivaara O, Knekt P, Aromaa A, Sievers K. Association of overweight, trauma and workload with coxarthrosis. A health survey of 7,217 persons. Acta Orthop Scand. 1993 Oct;64(5):513-8. doi: 10.3109/17453679308993681.

  PMID: 8237314 BACKGROUND

• Spector TD, Hart DJ, Doyle DV. Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity. Ann Rheum Dis. 1994 Sep;53(9):565-8. doi: 10.1136/ard.53.9.565.

  PMID: 7979593 BACKGROUND

• Jordan JM, Luta G, Renner JB, Linder GF, Dragomir A, Hochberg MC, Fryer JG. Self-reported functional status in osteoarthritis of the knee in a rural southern community: the role of sociodemographic factors, obesity, and knee pain. Arthritis Care Res. 1996 Aug;9(4):273-8. doi: 10.1002/1529-0131(199608)9:43.0.co;2-f.

  PMID: 8997916 BACKGROUND

• Woessner JF Jr. The family of matrix metalloproteinases. Ann N Y Acad Sci. 1994 Sep 6;732:11-21. doi: 10.1111/j.1749-6632.1994.tb24720.x. No abstract available.

  PMID: 7978784 BACKGROUND

• Tchetverikov I, Lohmander LS, Verzijl N, Huizinga TW, TeKoppele JM, Hanemaaijer R, DeGroot J. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 2005 May;64(5):694-8. doi: 10.1136/ard.2004.022434.

  PMID: 15834054 BACKGROUND

• Luan Y, Kong L, Howell DR, Ilalov K, Fajardo M, Bai XH, Di Cesare PE, Goldring MB, Abramson SB, Liu CJ. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis Cartilage. 2008 Nov;16(11):1413-20. doi: 10.1016/j.joca.2008.03.017. Epub 2008 May 15.

  PMID: 18485748 BACKGROUND

• Murphy G, Nagase H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol. 2008 Mar;4(3):128-35. doi: 10.1038/ncprheum0727.

  PMID: 18253109 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

1. 2cc whole blood to be collected from patient on date of total knee arthroplasty 2. Joint aspirate harvested and collected intraoperatively during total knee arhtroplasty

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Blood Specimen Collection; Phlebotomy

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Therapeutics

Study Officials

• Gaetano Scuderi, MD

  Stanford University, Dept. of Orthopedic Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 7, 2012
• Study Start: March 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 9, 2017

Record last verified: 2017-10

Locations

US (1)