Osteoarthritis of the KneeNCT01613833
Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints
An observational study of Osteoarthritis of the Knee, run by Scuderi, Gaetano J., M.D. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Osteoarthritis of the Knee
- What is being tested?
- Blood Draw and Joint Aspirate Harvest
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Aug 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing total knee arthroplasty
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Hospital
Palo Alto, California, 94304
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Osteoarthritis of the Knee
- Being tested
- Blood Draw, Joint Aspirate Harvest
- Keywords
- Alpha2 macroglobulin, Osteoarthritis, plasma and synovium
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood DrawProcedure or surgery
Also called Phlebotomy
Blood drawn for A2M levels to be assayed at Cytonics
Joint Aspirate HarvestProcedure or surgery
Also called Synoviual Fluid
Joint aspirate harvested for A2M levels to be assayed at Cytonics
Blood DrawProcedure or surgery
Also called Phlebotomy
Blood drawn for A2M levels to be assayed at Cytonics
Joint Aspirate HarvestProcedure or surgery
Also called Synovial Fluid
Joint aspirate harvested for A2M levels to be assayed at Cytonics
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Blood Draw; Procedure: Joint Aspirate Harvest |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Analyzed at the end of data collection within; approximately within 3 months of collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2012 (estimated)
- Study startMar 2012
- Primary completionAug 2018 (estimated)
- Study completionAug 2018 (estimated)
Why it stopped: need new PI, i moved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis of the KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Scuderi, Gaetano J., M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gaetano Scuderi, MD, Principal investigator, Stanford University, Dept. of Orthopedic Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01613833
- Sponsor's protocol ID
- Scu.Cyt.003
- Status last verified
- Oct 2017
- First submitted
- 5 Jun 2012
- Last updated
- 9 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Creamer P, Hochberg MC. Osteoarthritis. Lancet. 1997 Aug 16;350(9076):503-8. doi: 10.1016/S0140-6736(97)07226-7. No abstract available.
PubMed 9274595Heliovaara 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.
PubMed 8237314Spector 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.
PubMed 7979593Jordan 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.
PubMed 8997916Woessner 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.
PubMed 7978784Tchetverikov 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.
PubMed 15834054Luan 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.
PubMed 18485748Murphy 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.
PubMed 18253109
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints, and Comparison for Patients Undergoing Joint Replacement
- ClinicalTrials.gov ID
- NCT01613833
- Acronym / sponsor ID
- Scu.Cyt.003
- Conditions
- Osteoarthritis of the Knee
- Keywords
- Alpha2 macroglobulin, Osteoarthritis, plasma and synovium
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: need new PI, i moved
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Scuderi, Gaetano J., M.D.University, hospital or other
- Study start
- Mar 2012
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 7 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary OA Group | – | Procedure: Blood Draw, Procedure: Joint Aspirate HarvestSubjects 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. |
| Secondary/Post-traumatic OA Group | – | Procedure: Blood Draw, Procedure: Joint Aspirate HarvestSubjects who are to undergo primary total knee arthroplasty due to osteoarthritis of the knee that is secondary to injury or overuse of the joint. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing total knee arthroplasty
Key inclusion criteria (8 listed)
- 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
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood DrawAlso: PhlebotomyBlood drawn for A2M levels to be assayed at Cytonics | Procedure or surgery | Primary OA Group |
| Joint Aspirate HarvestAlso: Synoviual FluidJoint aspirate harvested for A2M levels to be assayed at Cytonics | Procedure or surgery | Primary OA Group |
| Blood DrawAlso: PhlebotomyBlood drawn for A2M levels to be assayed at Cytonics | Procedure or surgery | Secondary/Post-traumatic OA Group |
| Joint Aspirate HarvestAlso: Synovial FluidJoint aspirate harvested for A2M levels to be assayed at Cytonics | Procedure or surgery | Secondary/Post-traumatic OA Group |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2017.
- Background: PubMed 9274595Creamer P, Hochberg MC. Osteoarthritis. Lancet. 1997 Aug 16;350(9076):503-8. doi: 10.1016/S0140-6736(97)07226-7. No abstract available.
- Background: PubMed 8237314Heliovaara 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.
- Background: PubMed 7979593Spector 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.
- Background: PubMed 8997916Jordan 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.
- Background: PubMed 7978784Woessner 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.
- Background: PubMed 15834054Tchetverikov 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.
- Background: PubMed 18485748Luan 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.
- Background: PubMed 18253109Murphy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gaetano Scuderi, MD principal investigator
Stanford University, Dept. of Orthopedic Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoarthritis of the Knee, run by Scuderi, Gaetano J., M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 9 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A2M levels in plasma and synovium (time frame: Analyzed at the end of data collection within; approximately within 3 months of collection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01613833, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2017.