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

Scleroderma, Systemic Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01347008
• Other study ID #: FAPESP 2011/00012-3
• Status: Recruiting
• Phase: Phase 3
• First received: May 2, 2011
• Last updated: May 3, 2011
• Start date: April 2011
• Est. completion date: April 2012

Study information

• Verified date: April 2011
• Source: Federal University of São Paulo
• Contact: Fernando V Andrigueti, MD
• Phone: 55 11 55764239
• Email: fe_villela[@]yahoo.com.br
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Raynaud Phenomenon
• Scleroderma, Diffuse
• Scleroderma, Limited
• Scleroderma, Systemic

Intervention

Drug:
• Sildenafil citrate
Oral sildenafil citratre, 50mg b.i.d., 8 weeks
• Placebo
Placebo pills similar to sildenafil citrate pills, b.i.d for 8 weeks

Locations

Country	Name	City	State
Brazil	Systemic Sclerosis Outpatient Clinic, Hospital Sao Paulo, UNIFESP	Sao Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
Federal University of São Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Digital skin microvascular blood flow by means of Laser Doppler Imaging (LDI).		8 weeks	No
Secondary	Number and proliferative capacity of endothelial progenitor cells (EPC)		8 weeks	No
Secondary	Serum levels of vascular endothelial growth factor (VEGF)		8 weeks	No
Secondary	Clinical features of Raynaud's phenomenon and digital ulcers	Raynaud's Condition Score, HAQ and specific VAS scales for Raynaud's phenomenon and disability.	8 weeks	No