Clinical trial NCT01347008: Effect of Sildenafil on the Microcirculatory Blood Flow and Endothelial Progenitor Cells in Systemic Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Limited
Raynaud Phenomenon
Keywords: Sildenafil
Endothelial Progenitor Cells
Laser Doppler Imaging
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2011-05-04
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus
timeFrame: 8 weeks
measure: Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus.
timeFrame: 8 weeks
Secondary outcomes:
measure: Daily Frequency of Raynaud's Phenomenon Attacks
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Systemic Sclerosis Outpatient Clinic, Hospital Sao Paulo, UNIFESP
state: SP
Study officials:
affiliation: Federal University of São Paulo
name: Fernando V Andrigueti, MD
role: PRINCIPAL_INVESTIGATOR
References: