Estrogen Receptors and Chronic Venous Disease

Varicose Veins Clinical Trial

— ERCVD  

Official title:

Molecular Analysis of Estrogen Receptors in Patients With Chronic Venous Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02558426
• Other study ID #: ER.ALL.2013.31
• Status: Completed
• Phase: N/A
• First received: September 22, 2015
• Last updated: September 23, 2015
• Start date: January 2015
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: University of Cantanzaro
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial Summary

Chronic Venous Disease (CVD) is a very common problem affecting western adult population. To date the pathophysiology of CVD development encloses several theories such as the role of extracellular matrix (ECM) components alterations, the alteration of Matrix Metalloproteinases (MMPs) and other related molecules, the endothelial dysfunction, and several genetic factors but none of these could properly explain its genesis. Estrogen Receptors may be involved in CDV pathogenesis. Endogenous estrogens are important regulators of vascular homeostasis and they act mainly via three different ERs which are expressed in the cardiovascular system: ERα, ERβ, and a G protein-coupled estrogen receptor termed GPER. of this study is to explore the expression of estrogen receptors in vessel wall of varicose veins through the entire clinical spectrum of CVD.

Description:

Chronic Venous Disease (CVD) is a very common problem affecting western adult population with a prevalence of < 10%, among individuals younger than 30 years for both sex, and with a prevalence of 57% and 77%, in men and women aged ≥ 70 years respectively, and may be frequently associated with other clinical manifestations.

The spectrum of CVD ranges from varicose veins to leg edema, and serious dermal clinical manifestations consisting of hyperpigmentation, eczema, lipodermatosclerosis, and venous skin ulceration.

To date the pathophysiology of CVD development encloses several theories such as the role of extracellular matrix (ECM) components alterations, the alteration of Matrix Metalloproteinases (MMPs) and other related molecules, the endothelial dysfunction, and several genetic factors but none of these could properly explain its genesis.

A recent study (Serra R et al) showed a higher prevalence of CVD among patients with Breast Cancer (BC) respect to general population, especially in those patients that were positive to estrogen receptor (ER) expression.

The presence of ERs was investigated in the walls of normal and varicose veins by Mashiah A. et al, previously, and they documented that increased concentrations of estrogen receptors were found in varicose vein segments respect to healthy controls and this was particularly evident in females.

Endogenous estrogens are important regulators of vascular homeostasis and they act mainly via three different ERs which are expressed in the cardiovascular system: ERα, ERβ, and a G protein-coupled estrogen receptor termed GPER.

Although ERs are also suspected to be involved in the underlying etiology, the exact molecular mechanism responsible for development of CVD as well as the relationship with the wide range of clinical manifestations of CVD remains to be elucidated and the aim of this study is to explore the expression of estrogen receptors in vessel wall of varicose veins collected from patients with varicose veins through the entire clinical spectrum of CVD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with Chronic Venous Disease and varicose veins eligible to receive open venous surgery procedure

Exclusion Criteria:

• Concomitant Peripheral Artery Disease

• Previous Venous Thromboembolism

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Estrogen Excess
• Varicose Veins

Intervention

Procedure:
• Venous Surgery
Patients with Varicose Veins will undergo to venous surgery procedure. Samples obtained from patients undergoing surgical removal of varicose veins will be collected and immediately preserved at -80°. Briefly, the venous tissueswill be excised, homogenized with a motor-driven homogenizer and total RNA will be isolated using the Trizol reagent (Invitrogen, Milan, Italy), according to the manufacturer's instructions. The expression of ERa, ERß and GPER will be quantified by real-time PCR using the Step OneTM sequence detection system (Applied Biosystems Inc., Milan, Italy), following the manufacturer's instructions

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Cantanzaro

References & Publications (9)

de Franciscis S, Serra R. Matrix metalloproteinases and endothelial dysfunction: The search for new prognostic markers and for new therapeutic targets for vascular wall imbalance. Thromb Res. 2015 Jul;136(1):5-6. doi: 10.1016/j.thromres.2015.04.022. Epub 2015 Apr 24. — View Citation

Mashiah A, Berman V, Thole HH, Rose SS, Pasik S, Schwarz H, Ben-Hur H. Estrogen and progesterone receptors in normal and varicose saphenous veins. Cardiovasc Surg. 1999 Apr;7(3):327-31. — View Citation

Meyer MR, Prossnitz ER, Barton M. The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. Vascul Pharmacol. 2011 Jul-Sep;55(1-3):17-25. doi: 10.1016/j.vph.2011.06.003. Epub 2011 Jul 5. Review. — View Citation

Serra R, Buffone G, Costanzo G, Montemurro R, Perri P, Damiano R, de Franciscis S. Varicocele in younger as risk factor for inguinal hernia and for chronic venous disease in older: preliminary results of a prospective cohort study. Ann Vasc Surg. 2013 Apr;27(3):329-31. doi: 10.1016/j.avsg.2012.03.016. Epub 2012 Sep 19. — View Citation

Serra R, Buffone G, Costanzo G, Montemurro R, Scarcello E, Stillitano DM, Damiano R, de Franciscis S. Altered metalloproteinase-9 expression as least common denominator between varicocele, inguinal hernia, and chronic venous disorders. Ann Vasc Surg. 2014 Apr;28(3):705-9. doi: 10.1016/j.avsg.2013.07.026. Epub 2013 Oct 31. — View Citation

Serra R, Buffone G, de Franciscis A, Mastrangelo D, Molinari V, Montemurro R, de Franciscis S. A genetic study of chronic venous insufficiency. Ann Vasc Surg. 2012 Jul;26(5):636-42. doi: 10.1016/j.avsg.2011.11.036. — View Citation

Serra R, Buffone G, Falcone D, Molinari V, Scaramuzzino M, Gallelli L, de Franciscis S. Chronic venous leg ulcers are associated with high levels of metalloproteinases-9 and neutrophil gelatinase-associated lipocalin. Wound Repair Regen. 2013 May-Jun;21(3):395-401. doi: 10.1111/wrr.12035. Epub 2013 Mar 26. — View Citation

Serra R, Buffone G, Miglietta AM, Abonante S, Giordano V, Renne M, Lugarà M, de Franciscis S. Breast cancer and venous disease: a retrospective cohort study. Ann Vasc Surg. 2013 Aug;27(6):762-6. doi: 10.1016/j.avsg.2012.10.020. Epub 2013 Jul 1. — View Citation

Serra R, Gallelli L, Buffone G, Molinari V, Stillitano DM, Palmieri C, de Franciscis S. Doxycycline speeds up healing of chronic venous ulcers. Int Wound J. 2015 Apr;12(2):179-84. doi: 10.1111/iwj.12077. Epub 2013 Apr 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	expression of ERa, ERß and GPER	The expression of ERa, ERß and GPER will be quantified by real-time PCR using the Step OneTM sequence detection system (Applied Biosystems Inc., Milan, Italy), following the manufacturer's instructions	At month 9th	No