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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01347008
Recruitment Status : Completed
First Posted : May 4, 2011
Results First Posted : December 5, 2016
Last Update Posted : December 5, 2016
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Fernando Villela Andrigueti, Federal University of São Paulo

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.

Condition or disease Intervention/treatment Phase
Scleroderma, Systemic Scleroderma, Diffuse Scleroderma, Limited Raynaud Phenomenon Drug: Sildenafil citrate Drug: Placebo (Sugar pill) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : April 2011
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

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 Name: 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 Name: Placebo

Primary Outcome Measures :
  1. Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus [ Time Frame: 8 weeks ]
    Finger blood flow of the four medial fingers, measured by laser Doppler imaging and expressed in arbitrary perfusion units (p.u.).

  2. Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus. [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Daily Frequency of Raynaud's Phenomenon Attacks [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01347008

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Systemic Sclerosis Outpatient Clinic, Hospital Sao Paulo, UNIFESP
Sao Paulo, SP, Brazil
Sponsors and Collaborators
Federal University of São Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
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Principal Investigator: Fernando V Andrigueti, MD Federal University of Sao Paulo

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Responsible Party: Fernando Villela Andrigueti, MD, Federal University of São Paulo Identifier: NCT01347008    
Other Study ID Numbers: FAPESP 2011/00012-3
First Posted: May 4, 2011    Key Record Dates
Results First Posted: December 5, 2016
Last Update Posted: December 5, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Fernando Villela Andrigueti, Federal University of São Paulo:
Endothelial Progenitor Cells
Laser Doppler Imaging
Additional relevant MeSH terms:
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Raynaud Disease
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Scleroderma, Limited
Connective Tissue Diseases
Skin Diseases
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Sildenafil Citrate
Citric Acid
Sodium Citrate
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents