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Effect of sildenafil on the microcirculatory blood flow and on the endothelial progenitor cells in patients with systemic sclerosis: a randomized, double-blind, placebo-controlled clinical trial

Grant number: 11/00012-3
Support Opportunities:Regular Research Grants
Duration: March 01, 2011 - February 28, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Cristiane Kayser
Grantee:Cristiane Kayser
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated researchers:Fernando Villela Andrigueti


Progressive microangiopathy and endothelial dysfunction are identified in early phases of systemic sclerosis. These alterations may result in progressive reduction of vessel lumen, decreased blood flow, and a state of chronic hypoxia resulting in digital ulcers, digital pitting, and, in more severe cases, gangrene and amputation of the extremities. Few studies aimed to evaluate the effects of Sildenafil on the microcirculatory blood flow in patients with Raynaud's phenomenon secondary to systemic sclerosis (SS). Moreover, no study has evaluated the effect of this drug on the number and function of endothelial progenitor cells in SS patients. The relatively new technique of laser Doppler imaging (LDI) allows an objective measurement of superficial cutaneous microvascular blood flow and constitutes a promising approach in the assessment of the digital microvascular vasoreactivity in response to cold stimulus or in response to treatment in SSc patients. Objective: The present study aims to evaluate the effect of oral Sildenafil on the digital skin microvascular blood flow of SS patients with early disease (time of diagnosis < 4 years) by means of Laser Doppler Imaging (LDI). Secondary objectives: To examine the effects of oral sildenafil on the: (1) number and proliferative capacity of endothelial progenitor cells (EPC); (2) serum levels of vascular endothelial growth factor (VEGF); and (3) clinical features of Raynaud's phenomenon and digital ulcers. Methods: A randomized double-blind placebo controlled trial will be conducted. Forty four SSc patients will be randomly assigned to receive oral sildenafil 100mg/day or placebo for 8 weeks. The primary and secondary endpoints will be evaluated at baseline, after 8 weeks of treatment, and 2 weeks after the end of the treatment in all subjects. Skin blood flow of the dorsum of 4 fingertips (excluding the thumb) of the left hand will be measure using LDI (Moor LDI-VR, Moor Instruments, Axminster, UK) at baseline and for 30 minutes after cold stimulus, at all evaluations. EPCs will be assessed by means of flow cytometry and colony-forming units. VEGF levels will be assessed by comercial enzyme-linked immunosorbent assays (ELISA). The treatment of SSc vasculopathy remains a challenge. Expected results: The administration of oral Sildenafil could improve microvascular blood flow, as well as laboratory and clinical parameters, particularly in early phases of the disease, leading to a decrease in disease morbidity. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANDRIGUETI, FERNANDO V.; ARISMENDI, MARIA I.; EBBING, PAMELA C. C.; KAYSER, CRISTIANE. Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis. MICROVASCULAR RESEARCH, v. 98, p. 82-87, . (11/00012-3)

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