Metalloproteinase SNPs -1575 G/A MMP-2, 836 A/G MMP-9 and -77 A/G MMP-13 and Risk for Developing Knee Osteoarthritis in Greek PopulationNCT04463290
Association of Single Nucleotide Polymorphisms (SNPs) in Metalloproteinases (MMPs) Genes With the Risk of Primary Knee Osteoarthritis in Greek Population.
An observational study of Metalloproteinase SNPs -1575 G/A MMP-2, 836 A/G MMP-9 and -77 A/G MMP-13 and Risk for Developing Knee Osteoarthritis in Greek Population, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
Does the presence of gene polymorphisms -1575G / A in the MMP-2 gene, 836A / G in the MMP-9 gene and -77A / G in the MMP-13 gene, affect the risk of developing idiopathic knee osteoarthritis in the Greek population? Read more about this study
- Who is it for?
- Ages 55 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Metalloproteinase SNPs -1575 G/A MMP-2, 836 A/G MMP-9 and -77 A/G MMP-13 and Risk for Developing Knee Osteoarthritis in Greek Population
- How many people
- 200 participants
- Where
- 1 siteGreece
- Study dates
- 6 Jul 2020to 30 Dec 2022
- 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 55 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study will take place at the 3rd Orthopedic Department of Aristotle University of Thessaloniki of the Papageorgiou General Hospital of Thessaloniki. The patients group will be patients with primary knee osteoarthritis coming for first examination for knee pain or for sceduled total knee arthroplasty surgery. The control group will be people coming for examination due to accident (trauma, fracture) or anything else not relevant with knee pain. Both groups must not have any of the exclusion criteria
Who may be able to join
- Patients with primary knee osteoarthritis are selected based on clinical symptoms and radiological imaging with a score at least 2 on the Kellgren \& Lawrence scale.
- Patients without symptomatology or radiographic image of knee osteoarthritis (score <2 on Kellgren \& Lawrence scale) will be selected as controls.
Who cannot join
- systemic inflammatory disease
- rheumatic disease
- liver disease
- renal failure
- neoplasm or other chronic disease
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
3rd Orthopedic Department , Pagageorgiou Hospital
Thessaloniki, Athens, 56403
Christos Milaras, MD, +306942267715, mil1384@yahoo.gr
Eleftherios Tsiridis, Prof, +302313 323538, g.orthop@gmail.com
About this study
Does the presence of gene polymorphisms -1575G / A in the MMP-2 gene, 836A / G in the MMP-9 gene and -77A / G in the MMP-13 gene, affect the risk of developing idiopathic knee osteoarthritis in the Greek population?
Read the detailed description
This is a prospective case-control study in which the patients' genotype will be studied against the genotype of the controls. The study is prospective and not retrospective, as data will be collected from patients with primary knee osteoarthritis as well as the control group from the outset. The study intends to include 200 people. The first group consists of 100 individuals suffering from knee osteoarthritis, while the second group will include 100 healthy controls without osteoarthritis. From each one DNA will be isolated and analyzed from collected blood. The prospective study allows valid data to be collected on patient demographics and disease severity. Due to the large number of cases of the disease, it is estimated that the necessary specimens will be collected within a reasonable time from the beginning of this thesis. The choice of the patient-control study is necessary to limit the influence of confounding factors (age, gender, obesity, etc.). This type of study includes rigorous selection of patients and controls with specific entry and exclusion criteria, selection of controls based on matching patient characteristics, stratification, and subgroup analyzes. The final result will be a comparison of the incidence of specific gene polymorphisms between patients with knee osteoarthritis and the normal population.
- Being tested
- No intervention, Patients selection based on clinical symptoms and radiological imaging
- Keywords
- MMPs , SNPs, Knee osteoarthritis, -1575G/A MMP-2 , 836A/G MMP-9 , -77A/G MMP-13
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention, Patients selection based on clinical symptoms and radiological imagingOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Knee Osteoarthritis Patients Group | Patients suffering from primary knee osteoarthritis Receives: Other: No intervention, Patients selection based on clinical symptoms and radiological imaging | |
| Control Group | Healthy people without suffering from primary knee osteoarthritis Receives: Other: No intervention, Patients selection based on clinical symptoms and radiological imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
The frequency of presence of gene polymorphisms -1575G / A MMP-2 gene, 836A / G MMP-9 gene and -77A / G MMP-13 gene, in Greek patients with knee osteoarthritis comparing with healthy people
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start6 Jul 2020
- Primary completion28 Nov 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Metalloproteinase SNPs -1575 G/A MMP-2, 836 A/G MMP-9 and -77 A/G MMP-13 and Risk for Developing Knee Osteoarthritis in Greek PopulationStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christos Milaras, Aristotle University Of Thessaloniki
- Investigators
- Eleftherios Tsiridis, Professor, Study director, Aristotle University of Thessaloniki, 3rd Orthopaedic Department, Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463290
- Sponsor's protocol ID
- 197/17.6.2020
- Status last verified
- Aug 2022
- First submitted
- 5 Jul 2020
- Last updated
- 18 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data that will be shared will be all the demographic data of the participants (gender, age, etc.) and the study results data. Personal participants data as name, address, telephone number will not be shared for any reason.
Publications
Shi J, Son MY, Yamada S, Szabova L, Kahan S, Chrysovergis K, Wolf L, Surmak A, Holmbeck K. Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis. Dev Biol. 2008 Jan 1;313(1):196-209. doi: 10.1016/j.ydbio.2007.10.017. Epub 2007 Oct 23.
PubMed 18022611Hattori N, Mochizuki S, Kishi K, Nakajima T, Takaishi H, D'Armiento J, Okada Y. MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. Am J Pathol. 2009 Aug;175(2):533-46. doi: 10.2353/ajpath.2009.081080. Epub 2009 Jul 9.
PubMed 19590036Salo T, Makela M, Kylmaniemi M, Autio-Harmainen H, Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest. 1994 Feb;70(2):176-82.
PubMed 8139259Duerr S, Stremme S, Soeder S, Bau B, Aigner T. MMP-2/gelatinase A is a gene product of human adult articular chondrocytes and is increased in osteoarthritic cartilage. Clin Exp Rheumatol. 2004 Sep-Oct;22(5):603-8.
PubMed 15485014Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell. 1998 May 1;93(3):411-22. doi: 10.1016/s0092-8674(00)81169-1.
PubMed 9590175Soder S, Roach HI, Oehler S, Bau B, Haag J, Aigner T. MMP-9/gelatinase B is a gene product of human adult articular chondrocytes and increased in osteoarthritic cartilage. Clin Exp Rheumatol. 2006 May-Jun;24(3):302-4.
PubMed 16870098Dreier R, Grassel S, Fuchs S, Schaumburger J, Bruckner P. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 2004 Jul 15;297(2):303-12. doi: 10.1016/j.yexcr.2004.02.027.
PubMed 15212936Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res. 2015 Nov 23;14(4):14811-22. doi: 10.4238/2015.November.18.46.
PubMed 26600542Shiomi T, Lemaitre V, D'Armiento J, Okada Y. Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int. 2010 Jul;60(7):477-96. doi: 10.1111/j.1440-1827.2010.02547.x.
PubMed 20594269Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 2017 Nov 10;19(1):248. doi: 10.1186/s13075-017-1454-2.
PubMed 29126436Harendza S, Lovett DH, Panzer U, Lukacs Z, Kuhnl P, Stahl RA. Linked common polymorphisms in the gelatinase a promoter are associated with diminished transcriptional response to estrogen and genetic fitness. J Biol Chem. 2003 Jun 6;278(23):20490-9. doi: 10.1074/jbc.M211536200. Epub 2003 Mar 25.
PubMed 12657623Beber AR, Polina ER, Biolo A, Santos BL, Gomes DC, La Porta VL, Olsen V, Clausell N, Rohde LE, Santos KG. Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival. PLoS One. 2016 Aug 23;11(8):e0161666. doi: 10.1371/journal.pone.0161666. eCollection 2016.
PubMed 27551966Hua Y, Song L, Wu N, Xie G, Lu X, Fan X, Meng X, Gu D, Yang Y. Polymorphisms of MMP-2 gene are associated with systolic heart failure prognosis. Clin Chim Acta. 2009 Jun 27;404(2):119-23. doi: 10.1016/j.cca.2009.03.030. Epub 2009 Mar 28.
PubMed 19332048Morgan AR, Han DY, Thompson JM, Mitchell EA, Ferguson LR. Analysis of MMP2 promoter polymorphisms in childhood obesity. BMC Res Notes. 2011 Jul 21;4:253. doi: 10.1186/1756-0500-4-253.
PubMed 21777433Mossbock G, Weger M, Faschinger C, Zimmermann C, Schmut O, Renner W, El-Shabrawi Y. Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in open angle glaucomas. Mol Vis. 2010 Aug 28;16:1764-70.
PubMed 20808730
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of Single Nucleotide Polymorphisms (SNPs) in Metalloproteinases (MMPs) Genes With the Risk of Primary Knee Osteoarthritis in Greek Population.
- ClinicalTrials.gov ID
- NCT04463290
- Acronym / sponsor ID
- 197/17.6.2020
- Keywords
- MMPs , SNPs, Knee osteoarthritis, -1575G/A MMP-2 , 836A/G MMP-9 , -77A/G MMP-13
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 6 Jul 2020 (actual)
- Primary completion
- 28 Nov 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 9 Jul 2020 (actual)
- 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.
Does the presence of gene polymorphisms -1575G / A in the MMP-2 gene, 836A / G in the MMP-9 gene and -77A / G in the MMP-13 gene, affect the risk of developing idiopathic knee osteoarthritis in the Greek population?
Detailed description
This is a prospective case-control study in which the patients' genotype will be studied against the genotype of the controls. The study is prospective and not retrospective, as data will be collected from patients with primary knee osteoarthritis as well as the control group from the outset. The study intends to include 200 people. The first group consists of 100 individuals suffering from knee osteoarthritis, while the second group will include 100 healthy controls without osteoarthritis. From each one DNA will be isolated and analyzed from collected blood. The prospective study allows valid data to be collected on patient demographics and disease severity. Due to the large number of cases of the disease, it is estimated that the necessary specimens will be collected within a reasonable time from the beginning of this thesis. The choice of the patient-control study is necessary to limit the influence of confounding factors (age, gender, obesity, etc.). This type of study includes rigorous selection of patients and controls with specific entry and exclusion criteria, selection of controls based on matching patient characteristics, stratification, and subgroup analyzes. The final result will be a comparison of the incidence of specific gene polymorphisms between patients with knee osteoarthritis and the normal population.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Knee Osteoarthritis Patients Group | – | Other: No intervention, Patients selection based on clinical symptoms and radiological imagingPatients suffering from primary knee osteoarthritis |
| Control Group | – | Other: No intervention, Patients selection based on clinical symptoms and radiological imagingHealthy people without suffering from primary knee osteoarthritis |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study will take place at the 3rd Orthopedic Department of Aristotle University of Thessaloniki of the Papageorgiou General Hospital of Thessaloniki. The patients group will be patients with primary knee osteoarthritis coming for first examination for knee pain or for sceduled total knee arthroplasty surgery. The control group will be people coming for examination due to accident (trauma, fracture) or anything else not relevant with knee pain. Both groups must not have any of the exclusion criteria
Key inclusion criteria (2 listed)
- Patients with primary knee osteoarthritis are selected based on clinical symptoms and radiological imaging with a score at least 2 on the Kellgren \& Lawrence scale.
- Patients without symptomatology or radiographic image of knee osteoarthritis (score <2 on Kellgren \& Lawrence scale) will be selected as controls.
Key exclusion criteria (5 listed)
- systemic inflammatory disease
- rheumatic disease
- liver disease
- renal failure
- neoplasm or other chronic disease
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 |
|---|---|---|
| No intervention, Patients selection based on clinical symptoms and radiological imagingNo intervention | Other | Control Group, Knee Osteoarthritis Patients Group |
Primary outcome
The frequency of presence of gene polymorphisms -1575G / A MMP-2 gene, 836A / G MMP-9 gene and -77A / G MMP-13 gene, in Greek patients with knee osteoarthritis comparing with healthy people
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Background: PubMed 18022611Shi J, Son MY, Yamada S, Szabova L, Kahan S, Chrysovergis K, Wolf L, Surmak A, Holmbeck K. Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis. Dev Biol. 2008 Jan 1;313(1):196-209. doi: 10.1016/j.ydbio.2007.10.017. Epub 2007 Oct 23.
- Background: PubMed 19590036Hattori N, Mochizuki S, Kishi K, Nakajima T, Takaishi H, D'Armiento J, Okada Y. MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. Am J Pathol. 2009 Aug;175(2):533-46. doi: 10.2353/ajpath.2009.081080. Epub 2009 Jul 9.
- Background: PubMed 8139259Salo T, Makela M, Kylmaniemi M, Autio-Harmainen H, Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest. 1994 Feb;70(2):176-82.
- Background: PubMed 15485014Duerr S, Stremme S, Soeder S, Bau B, Aigner T. MMP-2/gelatinase A is a gene product of human adult articular chondrocytes and is increased in osteoarthritic cartilage. Clin Exp Rheumatol. 2004 Sep-Oct;22(5):603-8.
- Background: PubMed 9590175Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell. 1998 May 1;93(3):411-22. doi: 10.1016/s0092-8674(00)81169-1.
- Background: PubMed 16870098Soder S, Roach HI, Oehler S, Bau B, Haag J, Aigner T. MMP-9/gelatinase B is a gene product of human adult articular chondrocytes and increased in osteoarthritic cartilage. Clin Exp Rheumatol. 2006 May-Jun;24(3):302-4.
- Background: PubMed 15212936Dreier R, Grassel S, Fuchs S, Schaumburger J, Bruckner P. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 2004 Jul 15;297(2):303-12. doi: 10.1016/j.yexcr.2004.02.027.
- Background: PubMed 26600542Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res. 2015 Nov 23;14(4):14811-22. doi: 10.4238/2015.November.18.46.
- Background: PubMed 20594269Shiomi T, Lemaitre V, D'Armiento J, Okada Y. Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int. 2010 Jul;60(7):477-96. doi: 10.1111/j.1440-1827.2010.02547.x.
- Background: PubMed 29126436Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 2017 Nov 10;19(1):248. doi: 10.1186/s13075-017-1454-2.
- Background: PubMed 12657623Harendza S, Lovett DH, Panzer U, Lukacs Z, Kuhnl P, Stahl RA. Linked common polymorphisms in the gelatinase a promoter are associated with diminished transcriptional response to estrogen and genetic fitness. J Biol Chem. 2003 Jun 6;278(23):20490-9. doi: 10.1074/jbc.M211536200. Epub 2003 Mar 25.
- Background: PubMed 27551966Beber AR, Polina ER, Biolo A, Santos BL, Gomes DC, La Porta VL, Olsen V, Clausell N, Rohde LE, Santos KG. Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival. PLoS One. 2016 Aug 23;11(8):e0161666. doi: 10.1371/journal.pone.0161666. eCollection 2016.
- Individual participant dataSharing planned: Yes. The data that will be shared will be all the demographic data of the participants (gender, age, etc.) and the study results data. Personal participants data as name, address, telephone number will not be shared for any reason.
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.
Eleftherios Tsiridis, Professor study director
Aristotle University of Thessaloniki, 3rd Orthopaedic Department, Medical School
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 Metalloproteinase SNPs -1575 G/A MMP-2, 836 A/G MMP-9 and -77 A/G MMP-13 and Risk for Developing Knee Osteoarthritis in Greek Population, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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 2 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 18 Aug 2022. 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 Greece. 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?
Contact Christos Milaras, Phd Cand. (+306942267715, mil1384@yahoo.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The frequency of presence of gene polymorphisms -1575G / A MMP-2 gene, 836A / G MMP-9 gene and -77A / G MMP-13 gene, in Greek patients with knee osteoarthritis comparing with healthy people (time frame: 6 months). 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 NCT04463290, which also lists 25 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 18 Aug 2022.