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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Sildenafil citrate
* Drug: Placebo (Sugar pill)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil citrate<br>Oral Sildenafil citrate, 50mg, b.i.d. | Drug: Sildenafil citrate<br>* Oral sildenafil citratre, 50mg b.i.d., 8 weeks<br>* Other names: Sildenafil citrate, EMS Sigma Pharma, Ltd, Brazil;|
| Placebo Comparator: Sugar pill<br>Placebo pill (identical to Sildenafil citrate 50mg), b.i.d. | Drug: Placebo (Sugar pill)<br>* Placebo pills similar to sildenafil citrate pills, b.i.d for 8 weeks<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Frequency of Raynaud's Phenomenon Attacks | 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. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sildenafil, Endothelial Progenitor Cells, Laser Doppler Imaging