Ignite Creation Date:
2025-12-25 @ 2:44 AM
Ignite Modification Date:
2026-01-09 @ 4:23 PM
Study NCT ID:
NCT01613833
Status:
SUSPENDED
Last Update Posted:
2017-10-09
First Post:
2012-06-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020370', 'term': 'Osteoarthritis, Knee'}, {'id': 'D010003', 'term': 'Osteoarthritis'}], 'ancestors': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D012216', 'term': 'Rheumatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}, {'id': 'D018962', 'term': 'Phlebotomy'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': '1. 2cc whole blood to be collected from patient on date of total knee arthroplasty\n2. Joint aspirate harvested and collected intraoperatively during total knee arhtroplasty'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'whyStopped': 'need new PI, i moved', 'overallStatus': 'SUSPENDED', 'startDateStruct': {'date': '2012-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-10', 'completionDateStruct': {'date': '2018-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2017-10-06', 'studyFirstSubmitDate': '2012-06-05', 'studyFirstSubmitQcDate': '2012-06-05', 'lastUpdatePostDateStruct': {'date': '2017-10-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2012-06-07', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-08', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'A2M levels in plasma and synovium', 'timeFrame': 'Analyzed at the end of data collection within; approximately within 3 months of collection', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Alpha2 macroglobulin', 'Osteoarthritis', 'plasma and synovium'], 'conditions': ['Osteoarthritis of the Knee']}, 'referencesModule': {'references': [{'pmid': '9274595', 'type': 'BACKGROUND', 'citation': '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': '8237314', 'type': 'BACKGROUND', 'citation': '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': '7979593', 'type': 'BACKGROUND', 'citation': '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': '8997916', 'type': 'BACKGROUND', 'citation': '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': '7978784', 'type': 'BACKGROUND', 'citation': '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': '15834054', 'type': 'BACKGROUND', 'citation': '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': '18485748', 'type': 'BACKGROUND', 'citation': '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': '18253109', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nOA 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.\n\nMatrix 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.\n\nThis 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.', 'detailedDescription': 'This is a single institution observational study.\n\nPre-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.\n\nOn 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.\n\nOn 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '19 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients undergoing total knee arthroplasty', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nGroup 1, Non-traumatic primary OA:\n\n1. Subject scheduled to undergo primary unilateral total knee arthroplasty for primary osteoarthritis as determined by an orthopedic surgeon\n2. Subject is male or female over 45-75 years of age\n3. Subject is able to read and understand informed consent form and must subsequently sign and date consent form\n\nGroup 2, Secondary post-traumatic/overuse OA:\n\n1. 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.\n2. Subject is male or female 45-75 years of age\n3. Subject is able to read and understand informed consent form and must subsequently sign and date consent form\n\nExclusion Criteria:\n\nGroup 1, Non-traumatic primary OA:\n\n1. History of inflammatory arthritis (e.g. rheumatoid arthritis, ankylosing spondylitis)\n2. Indication for surgery other than osteoarthritis\n3. Revision total knee arthroplasty\n4. Age \\>75, age \\<44\n5. Unable to read, understand, or sign informed consent form\n6. Previous knee infection\n7. Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease\n\nGroup 2, Secondary post-traumatic/overuse OA:\n\n1. History of inflammatory arthritis (e.g. rheumatoid arthritis, ankyolosing spondylitis)\n2. Indication for surgery other than osteoarthritis\n3. Age \\>75, age \\<44\n4. Unable to read, understand, or sign informed consent form\n5. Previous knee infection\n6. Congenital disorders of the knee, calcium pyrophosphate dehydrate deposition disease'}, 'identificationModule': {'nctId': 'NCT01613833', 'briefTitle': 'Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints', 'organization': {'class': 'OTHER', 'fullName': 'Scuderi, Gaetano J., M.D.'}, 'officialTitle': 'Evaluation of Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints, and Comparison for Patients Undergoing Joint Replacement', 'orgStudyIdInfo': {'id': 'Scu.Cyt.003'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Primary OA Group', 'description': '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.', 'interventionNames': ['Procedure: Blood Draw', 'Procedure: Joint Aspirate Harvest']}, {'label': 'Secondary/Post-traumatic OA Group', 'description': '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.', 'interventionNames': ['Procedure: Blood Draw', 'Procedure: Joint Aspirate Harvest']}], 'interventions': [{'name': 'Blood Draw', 'type': 'PROCEDURE', 'otherNames': ['Phlebotomy'], 'description': 'Blood drawn for A2M levels to be assayed at Cytonics', 'armGroupLabels': ['Primary OA Group']}, {'name': 'Joint Aspirate Harvest', 'type': 'PROCEDURE', 'otherNames': ['Synoviual Fluid'], 'description': 'Joint aspirate harvested for A2M levels to be assayed at Cytonics', 'armGroupLabels': ['Primary OA Group']}, {'name': 'Blood Draw', 'type': 'PROCEDURE', 'otherNames': ['Phlebotomy'], 'description': 'Blood drawn for A2M levels to be assayed at Cytonics', 'armGroupLabels': ['Secondary/Post-traumatic OA Group']}, {'name': 'Joint Aspirate Harvest', 'type': 'PROCEDURE', 'otherNames': ['Synovial Fluid'], 'description': 'Joint aspirate harvested for A2M levels to be assayed at Cytonics', 'armGroupLabels': ['Secondary/Post-traumatic OA Group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94304', 'city': 'Palo Alto', 'state': 'California', 'country': 'United States', 'facility': 'Stanford University Hospital', 'geoPoint': {'lat': 37.44188, 'lon': -122.14302}}], 'overallOfficials': [{'name': 'Gaetano Scuderi, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Stanford University, Dept. of Orthopedic Surgery'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Scuderi, Gaetano J., M.D.', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}