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

October 6, 2017 updated by: Scuderi, Gaetano J., M.D.

Evaluation of Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints, and Comparison for Patients Undergoing Joint Replacement

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

This is a single institution observational study.

Pre-procedure diagnosis: Based on chart review and consultation with operating surgeon of subjects undergoing total knee arthroplasty, patients will be grouped into primary or secondary (PTOA) osteoarthritis groups. Primary osteoarthritis will be identified through a clinical presentation of generalized osteoarthritis with possible bilateral involvement and no identifiable trauma or overuse to knee joint. Secondary osteoarthritis will be identified by history of overuse or trauma to the afflicted knee and a clinical presentation that in general lacks symmetrical involvement and/or severity, PTOA.

On the date of surgery, both primary and secondary groups will have 2 cc whole blood collected via venipuncture during placement of intravenous access for anesthesia. No additional venipuncture is necessary and this study necessitates no instrumentation/manipulation of patient beyond that of IV access normally obtained preoperatively. Blood will then be placed in refrigerated storage (2-6 C) until analyzed for A2M assay.

On the date of surgery, joint aspirate from both primary and secondary groups will be collected by the operating surgeon during knee arthroplasty. At the time of arthrotomy, joint fluid that is expressed from surgical site will be harvested and placed into an eppendorf tube and placed on ice. The study incurs no further risk to the patient and no further instrumentation/manipulation for synovial fluid harvest that is beyond the risk or instrumentation/manipulation of the indicated surgical procedure. Joint aspirates will then be stored until A2M assay.

Study Type

Observational

Enrollment (Anticipated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients undergoing total knee arthroplasty

Description

Inclusion Criteria:

Group 1, Non-traumatic primary OA:

  1. Subject scheduled to undergo primary unilateral total knee arthroplasty for primary osteoarthritis as determined by an orthopedic surgeon
  2. Subject is male or female over 45-75 years of age
  3. 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:

  1. 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.
  2. Subject is male or female 45-75 years of age
  3. Subject is able to read and understand informed consent form and must subsequently sign and date consent form

Exclusion Criteria:

Group 1, Non-traumatic primary OA:

  1. History of inflammatory arthritis (e.g. rheumatoid arthritis, ankylosing spondylitis)
  2. Indication for surgery other than osteoarthritis
  3. Revision total knee arthroplasty
  4. Age >75, age <44
  5. Unable to read, understand, or sign informed consent form
  6. Previous knee infection
  7. Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease

Group 2, Secondary post-traumatic/overuse OA:

  1. History of inflammatory arthritis (e.g. rheumatoid arthritis, ankyolosing spondylitis)
  2. Indication for surgery other than osteoarthritis
  3. Age >75, age <44
  4. Unable to read, understand, or sign informed consent form
  5. Previous knee infection
  6. Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
Blood drawn for A2M levels to be assayed at Cytonics
Other Names:
  • Phlebotomy
Procedure: Joint Aspirate Harvest
Joint aspirate harvested for A2M levels to be assayed at Cytonics
Other Names:
  • Synovial Fluid
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
Blood drawn for A2M levels to be assayed at Cytonics
Other Names:
  • Phlebotomy
Procedure: Joint Aspirate Harvest
Joint aspirate harvested for A2M levels to be assayed at Cytonics
Other Names:
  • Synovial Fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A2M levels in plasma and synovium
Time Frame: Analyzed at the end of data collection within; approximately within 3 months of collection
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Scuderi, Gaetano J., M.D.

Investigators

  • Principal Investigator: Gaetano Scuderi, MD, Stanford University, Dept. of Orthopedic Surgery

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (ANTICIPATED)

August 1, 2018

Study Completion (ANTICIPATED)

August 1, 2018

Study Registration Dates

First Submitted

June 5, 2012

First Submitted That Met QC Criteria

June 5, 2012

First Posted (ESTIMATE)

June 7, 2012

Study Record Updates

Last Update Posted (ACTUAL)

October 9, 2017

Last Update Submitted That Met QC Criteria

October 6, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Scu.Cyt.003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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