Osteoarthritis, KneeNCT00850538
Role of Bone in Knee Osteoarthritis (OA)
An observational study of Osteoarthritis, Knee, run by The New England Baptist Hospital at 1 site in Australia.
Trial summary
The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- MRI and Primary Total Knee Replacement
- Type of treatment
- Surgery or procedure
- How many people
- 101 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2008to Apr 2013
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Male or female, over age 18, with scheduled primary total knee replacement surgery at NEBH, with no contradindications for MRI
Who may be able to join
- subjects having primary knee replacement surgery with 1 participating surgeon at NEBH (principal investigator)
Who cannot join
- subjects having a revision knee replacement instead of a primary knee replacement
- contraindications for MRI
- pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Bone and Its Measurement in Knee Osteoarthritis
The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. Connective tissues including tendon, ligament, and meniscus specimens normally discarded from total joint replacements will be used for live cell harvest, and protein and gene expression analyses of tissue or cultured cells.
Read the detailed description
BACKGROUND AND SIGNIFICANCE:
Although the presence of bone marrow lesions (BML) on MRI is strongly associated with osteoarthritis (OA) progression and pain in some studies, the mechanism for this relation and the underlying pathology is not well established. The lack of knowledge on what these lesions constitute hampers their clinical utility both with regards to measurement and targeting for therapeutic intervention.
Our preliminary data has localized specific changes in bone mineralization, remodeling and defects within BML features that are adjacent to the subchondral plate. BMLs appear to be sclerotic compared to unaffected regions; however, the mineral density in these lesions is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition. Limited histological analysis of BMLs reveal thrombi, diffuse fibrinoid necrosis and hyperplasia of blood vessel walls - all indicative of infarction-like pathology.
The aim of this research proposal is to create more specific targets and improve our understanding of the pathology in BMLs.
Specific Aim 1:
- To collect tissue to evaluate protein and gene expression of these tissues and cultured cells.
- Conditions
- Osteoarthritis, Knee
- Being tested
- MRI, Primary Total Knee Replacement
- Keywords
- Bone Marrow Lesion, BML, Arthroplasty, Replacement, Knee, Discarded tissue
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIRadiation
1.5T MRI exam of signal knee with knee coil (estimated time: 35 minutes)
Primary Total Knee ReplacementProcedure or surgery
Fluid, bone, and meniscus specimens obtained from total joint replacement will be collected.
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Viable Specimens for Genetic Analysis
Measured: Tissue samples collected at time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2009 (estimated)
- Study startJul 2008
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, 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
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- The New England Baptist Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Hunter, The New England Baptist Hospital
- Investigators
- David Hunter, MD, Principal investigator, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00850538
- Sponsor's protocol ID
- NEBH 2008-018
- Status last verified
- Nov 2015
- First submitted
- 23 Feb 2009
- Last updated
- 4 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Burr DB. The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 2004 Apr;70:77-80. No abstract available.
PubMed 15132360Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, Kazis L, Gale DR. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001 Apr 3;134(7):541-9. doi: 10.7326/0003-4819-134-7-200104030-00007.
PubMed 11281736Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, Li W, Hill C, Gale D. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med. 2003 Sep 2;139(5 Pt 1):330-6. doi: 10.7326/0003-4819-139-5_part_1-200309020-00008.
PubMed 12965941Lo GH, Hunter DJ, Zhang Y, McLennan CE, Lavalley MP, Kiel DP, McLean RR, Genant HK, Guermazi A, Felson DT. Bone marrow lesions in the knee are associated with increased local bone density. Arthritis Rheum. 2005 Sep;52(9):2814-21. doi: 10.1002/art.21290.
PubMed 16145676Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, Guermazi A, Genant H, Gale D, Felson DT. Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum. 2006 May;54(5):1529-35. doi: 10.1002/art.21789.
PubMed 16646037Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000 Jun;215(3):835-40. doi: 10.1148/radiology.215.3.r00jn05835.
PubMed 10831707Neuhold A, Hofmann S, Engel A, Leder K, Kramer J, Haller J, Plenk H. Bone marrow edema of the hip: MR findings after core decompression. J Comput Assist Tomogr. 1992 Nov-Dec;16(6):951-5. doi: 10.1097/00004728-199211000-00023.
PubMed 1430447Plenk H Jr, Hofmann S, Eschberger J, Gstettner M, Kramer J, Schneider W, Engel A. Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip. Clin Orthop Relat Res. 1997 Jan;(334):73-84.
PubMed 9005898Reinus WR, Fischer KC, Ritter JH. Painful transient tibial edema. Radiology. 1994 Jul;192(1):195-9. doi: 10.1148/radiology.192.1.8208937.
PubMed 8208937Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis. 2008 Feb;67(2):206-11. doi: 10.1136/ard.2006.066183. Epub 2007 May 1.
PubMed 17472995Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG, Carter WO, Hellio Le Graverand MP, Kloppenburg M. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology. 2006 Jun;239(3):811-7. doi: 10.1148/radiol.2393050253.
PubMed 16714463Hayes CW, Jamadar DA, Welch GW, Jannausch ML, Lachance LL, Capul DC, Sowers MR. Osteoarthritis of the knee: comparison of MR imaging findings with radiographic severity measurements and pain in middle-aged women. Radiology. 2005 Dec;237(3):998-1007. doi: 10.1148/radiol.2373041989. Epub 2005 Oct 26.
PubMed 16251398Simkin PA. Bone pain and pressure in osteoarthritic joints. Novartis Found Symp. 2004;260:179-86; discussion 186-90, 277-9.
PubMed 15283450Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, Keyser CP, Clohisy DR, Adams DJ, O'Leary P, Mantyh PW. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience. 2002;113(1):155-66. doi: 10.1016/s0306-4522(02)00165-3.
PubMed 12123694Hukkanen M, Konttinen YT, Rees RG, Gibson SJ, Santavirta S, Polak JM. Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers. J Rheumatol. 1992 Aug;19(8):1252-9.
PubMed 1383542
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Bone and Its Measurement in Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT00850538
- Acronym / sponsor ID
- NEBH 2008-018
- Conditions
- Osteoarthritis, Knee
- Keywords
- Bone Marrow Lesion, BML, Arthroplasty, Replacement, Knee, Discarded tissue
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- The New England Baptist HospitalUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 25 Feb 2009 (estimated)
- Results
- Posted 4 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. Connective tissues including tendon, ligament, and meniscus specimens normally discarded from total joint replacements will be used for live cell harvest, and protein and gene expression analyses of tissue or cultured cells.
Detailed description
BACKGROUND AND SIGNIFICANCE:
Although the presence of bone marrow lesions (BML) on MRI is strongly associated with osteoarthritis (OA) progression and pain in some studies, the mechanism for this relation and the underlying pathology is not well established. The lack of knowledge on what these lesions constitute hampers their clinical utility both with regards to measurement and targeting for therapeutic intervention.
Our preliminary data has localized specific changes in bone mineralization, remodeling and defects within BML features that are adjacent to the subchondral plate. BMLs appear to be sclerotic compared to unaffected regions; however, the mineral density in these lesions is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition. Limited histological analysis of BMLs reveal thrombi, diffuse fibrinoid necrosis and hyperplasia of blood vessel walls - all indicative of infarction-like pathology.
The aim of this research proposal is to create more specific targets and improve our understanding of the pathology in BMLs.
Specific Aim 1:
- To collect tissue to evaluate protein and gene expression of these tissues and cultured cells.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Male or female, over age 18, with scheduled primary total knee replacement surgery at NEBH, with no contradindications for MRI
Key inclusion criteria (1 listed)
- subjects having primary knee replacement surgery with 1 participating surgeon at NEBH (principal investigator)
Key exclusion criteria (3 listed)
- subjects having a revision knee replacement instead of a primary knee replacement
- contraindications for MRI
- pregnancy
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 |
|---|---|---|
| MRI1.5T MRI exam of signal knee with knee coil (estimated time: 35 minutes) | Radiation | – |
| Primary Total Knee ReplacementFluid, bone, and meniscus specimens obtained from total joint replacement will be collected. | Procedure or surgery | – |
Primary outcome
Number of Participants With Viable Specimens for Genetic Analysis
Time frame: Tissue samples collected at time of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15132360Burr DB. The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 2004 Apr;70:77-80. No abstract available.
- Background: PubMed 11281736Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, Kazis L, Gale DR. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001 Apr 3;134(7):541-9. doi: 10.7326/0003-4819-134-7-200104030-00007.
- Background: PubMed 12965941Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, Li W, Hill C, Gale D. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med. 2003 Sep 2;139(5 Pt 1):330-6. doi: 10.7326/0003-4819-139-5_part_1-200309020-00008.
- Background: PubMed 16145676Lo GH, Hunter DJ, Zhang Y, McLennan CE, Lavalley MP, Kiel DP, McLean RR, Genant HK, Guermazi A, Felson DT. Bone marrow lesions in the knee are associated with increased local bone density. Arthritis Rheum. 2005 Sep;52(9):2814-21. doi: 10.1002/art.21290.
- Background: PubMed 16646037Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, Guermazi A, Genant H, Gale D, Felson DT. Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum. 2006 May;54(5):1529-35. doi: 10.1002/art.21789.
- Background: PubMed 10831707Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000 Jun;215(3):835-40. doi: 10.1148/radiology.215.3.r00jn05835.
- Background: PubMed 1430447Neuhold A, Hofmann S, Engel A, Leder K, Kramer J, Haller J, Plenk H. Bone marrow edema of the hip: MR findings after core decompression. J Comput Assist Tomogr. 1992 Nov-Dec;16(6):951-5. doi: 10.1097/00004728-199211000-00023.
- Background: PubMed 9005898Plenk H Jr, Hofmann S, Eschberger J, Gstettner M, Kramer J, Schneider W, Engel A. Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip. Clin Orthop Relat Res. 1997 Jan;(334):73-84.
- Background: PubMed 8208937Reinus WR, Fischer KC, Ritter JH. Painful transient tibial edema. Radiology. 1994 Jul;192(1):195-9. doi: 10.1148/radiology.192.1.8208937.
- Background: PubMed 17472995Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis. 2008 Feb;67(2):206-11. doi: 10.1136/ard.2006.066183. Epub 2007 May 1.
- Background: PubMed 16714463Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG, Carter WO, Hellio Le Graverand MP, Kloppenburg M. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology. 2006 Jun;239(3):811-7. doi: 10.1148/radiol.2393050253.
- Background: PubMed 16251398Hayes CW, Jamadar DA, Welch GW, Jannausch ML, Lachance LL, Capul DC, Sowers MR. Osteoarthritis of the knee: comparison of MR imaging findings with radiographic severity measurements and pain in middle-aged women. Radiology. 2005 Dec;237(3):998-1007. doi: 10.1148/radiol.2373041989. Epub 2005 Oct 26.
- New England Baptist Hospital WebsiteLink provided by the sponsor.
Related trials for Osteoarthritis, Knee
Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
Recruiting
Effect of Anti-inflammatory Diet in Osteoarthritis
Osteoarthritis, Knee
Active, not recruitingPhase 2/3
Single vs Triple Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis, Knee
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
RecruitingObservational study
Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.
Knee Osteoarthritis
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.
David Hunter, MD principal investigator
University of Sydney
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, Knee, run by The New England Baptist Hospital at 1 site in Australia.
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 1 inclusion and 3 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: finished, as of the sponsor's last update on 4 Dec 2015. 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 Australia. 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?
Yes. Results are posted in the registry (first posted 4 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Viable Specimens for Genetic Analysis (time frame: Tissue samples collected at time of surgery). 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 NCT00850538, which also lists 16 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 4 Dec 2015.