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

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

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.

Study Overview

• Status: Completed
• Conditions: Scleroderma, Systemic; Scleroderma, Diffuse; Raynaud Phenomenon; Scleroderma, Limited
• Intervention / Treatment: Drug: Sildenafil citrate; Drug: Placebo (Sugar pill)

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil
      • Systemic Sclerosis Outpatient Clinic, Hospital Sao Paulo, UNIFESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Fernando V Andrigueti, MD, Federal University of São Paulo

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 2, 2011
• First Submitted That Met QC Criteria: May 3, 2011
• First Posted (Estimate): May 4, 2011

Study Record Updates

• Last Update Posted (Estimate): December 5, 2016
• Last Update Submitted That Met QC Criteria: October 12, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Sildenafil; Endothelial Progenitor Cells; Laser Doppler Imaging
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Connective Tissue Diseases; Peripheral Vascular Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Raynaud Disease; Scleroderma, Limited; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Anticoagulants; Phosphodiesterase Inhibitors; Chelating Agents; Sequestering Agents; Phosphodiesterase 5 Inhibitors; Calcium Chelating Agents; Sildenafil Citrate; Citric Acid; Sodium Citrate
• Other Study ID Numbers: FAPESP 2011/00012-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No