Effect of Sildenafil on the Microcirculatory Blood Flow and Endothelial Progenitor Cells in Systemic Sclerosis

Phase 3

Completed

Conditions: Scleroderma, Diffuse
Scleroderma, Systemic
Scleroderma, Limited
Raynaud Phenomenon

Brief Summary: Early phases of systemic sclerosis is characterized by inflammatory and microvasculature alterations. Sildenafil citrate has been shown to have vasodilatory effects and to enhance vasculogenesis. The purpose of this study is to evaluate the effect of sildenafil citrate on hand blood flow of patients with systemic sclerosis, using Laser Doppler Imaging.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Systemic sclerosis according to the classification criteria of the American College of Rheumatology (1980) with no more than 4 years since diagnosis
Early systemic sclerosis as defined by LeRoy and Medsger (2001)
6 or more Raynaud's crisis per week
Written informed consent provided by the subjects prior to initiating study procedures

Exclusion Criteria

Smoking
Peripheral or central vasculopathy other than Systemic sclerosis
Uncontrolled Diabetes
Liver disease
Pregnant or lactating woman
Current use of cyclosporin, prostanoids, bosentan or any PDE-5 inhibitors (including current Sildenafil use during randomization)
History of stroke, myocardial infarction or life threatening cardiac condition within the last 6 months
History of surgical sympathectomy
Systolic blood pressure < 85mm Hg
History of scleroderma renal crisis
Known hypersensitivity to Sildenafil or any of the excipients
History of Retinitis Pigmentosa
Current use of Nitrates

Arm && Interventions

Group	Intervention	Description
Sildenafil citrate	Sildenafil citrate	Oral Sildenafil citrate, 50mg, b.i.d.
Sugar pill	Placebo (Sugar pill)	Placebo pill (identical to Sildenafil citrate 50mg), b.i.d.

Primary Outcome Measures

Name	Time	Method
Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus	8 weeks	Finger blood flow of the four medial fingers, measured by laser Doppler imaging and expressed in arbitrary perfusion units (p.u.).
Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus.	8 weeks

Secondary Outcome Measures

Name	Time	Method
Daily Frequency of Raynaud's Phenomenon Attacks	8 weeks	Daily frequency of RP attacks as self registered in a 1-week diary. Any episode of pallor or cyanosis of the hand/fingers was considered as a RP attack, and patients were supposed to register the daily amount of such episodes on a 1-week diary, previously to the medical visit.