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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04463290
Other study ID # 197/17.6.2020
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date July 6, 2020
Est. completion date December 30, 2022

Study information

Verified date August 2022
Source Aristotle University Of Thessaloniki
Contact Christos Milaras, Phd Cand.
Phone +306942267715
Email mil1384@yahoo.gr
Is FDA regulated No
Health authority
Study type Observational

Clinical 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?


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date December 30, 2022
Est. primary completion date November 28, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 55 Years to 80 Years
Eligibility Inclusion Criteria: - 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. Exclusion Criteria: - systemic inflammatory disease - rheumatic disease - liver disease - renal failure - neoplasm or other chronic disease

Study Design


Related Conditions & MeSH terms

  • 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
  • Osteoarthritis
  • Osteoarthritis, Knee

Intervention

Other:
No intervention, Patients selection based on clinical symptoms and radiological imaging
No intervention

Locations

Country Name City State
Greece 3rd Orthopedic Department , Pagageorgiou Hospital Thessaloníki Athens

Sponsors (1)

Lead Sponsor Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

References & Publications (25)

Štrbac D, Goricar K, Dolžan V, Kovac V. Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma. Dis Markers. 2017;2017:8069529. doi: 10.1155/2017/8069529. Epub 2017 Sep 12. — View Citation

Beber 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. — View Citation

Chen X, Chen Y, Wiggs JL, Pasquale LR, Sun X, Fan BJ. Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma. PLoS One. 2016 Jun 7;11(6):e0157093. doi: 10.1371/journal.pone.0157093. eCollection 2016. — View Citation

Dreier R, Grässel 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. — View Citation

Duerr 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. — View Citation

Harendza 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. Epub 2003 Mar 25. — View Citation

Hattori 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. — View Citation

Hua 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. — View Citation

Li 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. Review. — View Citation

Morgan 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. — View Citation

Mossböck 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. — View Citation

Park YS, Jeon YJ, Kim HS, Han IB, Oh SH, Kim DS, Kim NK. The GC + CC genotype at position -418 in TIMP-2 promoter and the -1575GA/-1306CC genotype in MMP-2 is genetic predisposing factors for prevalence of moyamoya disease. BMC Neurol. 2014 Oct 4;14:180. doi: 10.1186/s12883-014-0180-5. — View Citation

Pérez-Hernández N, Vargas-Alarcón G, Martínez-Rodríguez N, Martínez-Ríos MA, Peña-Duque MA, Peña-Díaz Ade L, Valente-Acosta B, Posadas-Romero C, Medina A, Rodríguez-Pérez JM. The matrix metalloproteinase 2-1575 gene polymorphism is associated with the risk of developing myocardial infarction in Mexican patients. J Atheroscler Thromb. 2012;19(8):718-27. Epub 2012 Jun 27. — View Citation

Rose BJ, Kooyman DL. A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology. Dis Markers. 2016;2016:4895050. doi: 10.1155/2016/4895050. Epub 2016 Jul 13. Review. — View Citation

Sabbatini AR, Barbaro NR, de Faria AP, Ritter AMV, Modolo R, Correa NB, Brunelli V, Pinho C, Fontana V, Moreno H. Matrix metalloproteinase-2 -735C/T polymorphism is associated with resistant hypertension in a specialized outpatient clinic in Brazil. Gene. 2017 Jul 15;620:23-29. doi: 10.1016/j.gene.2017.04.004. Epub 2017 Apr 5. — View Citation

Salo T, Mäkelä M, Kylmäniemi 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. — View Citation

Saravani S, Yari D, Saravani R, Azadi Ahmadabadi C. Association of COL4A3 (rs55703767), MMP-9 (rs17576)and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes. Biomed Rep. 2017 Mar;6(3):329-334. doi: 10.3892/br.2017.856. Epub 2017 Feb 9. — View Citation

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. Epub 2007 Oct 23. — View Citation

Shiomi T, Lemaître 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. Review. — View Citation

Söder 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. — View Citation

Takashiba S, Naruishi K. Gene polymorphisms in periodontal health and disease. Periodontol 2000. 2006;40:94-106. Review. — View Citation

Vu 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. — View Citation

Wu HD, Bai X, Chen DM, Cao HY, Qin L. Association of genetic polymorphisms in matrix metalloproteinase-9 and coronary artery disease in the Chinese Han population: a case-control study. Genet Test Mol Biomarkers. 2013 Sep;17(9):707-12. doi: 10.1089/gtmb.2013.0109. Epub 2013 Jul 2. — View Citation

Yoon S, Kuivaniemi H, Gatalica Z, Olson JM, Butticè G, Ye S, Norris BA, Malcom GT, Strong JP, Tromp G. MMP13 promoter polymorphism is associated with atherosclerosis in the abdominal aorta of young black males. Matrix Biol. 2002 Oct;21(6):487-98. — View Citation

Zeng 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. — View Citation

* Note: There are 25 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 6 months