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

This study has been completed.
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Fernando Villela Andrigueti, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT01347008
First received: May 2, 2011
Last updated: October 12, 2016
Last verified: October 2016
  Purpose
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 Intervention Phase
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Limited
Raynaud Phenomenon
Drug: Sildenafil citrate
Drug: Placebo (Sugar pill)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Finger blood flow of the four medial fingers, measured by laser Doppler imaging and expressed in arbitrary perfusion units (p.u.).

  • Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Daily Frequency of Raynaud's Phenomenon Attacks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 41
Study Start Date: April 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01347008

Locations
Brazil
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
Investigators
Principal Investigator: Fernando V Andrigueti, MD Federal University of Sao Paulo
  More Information

Responsible Party: Fernando Villela Andrigueti, MD, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT01347008     History of Changes
Other Study ID Numbers: FAPESP 2011/00012-3 
Study First Received: May 2, 2011
Results First Received: August 20, 2016
Last Updated: October 12, 2016
Health Authority: Brazil: National Committee of Ethics in Research
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Federal University of São Paulo:
Sildenafil
Endothelial Progenitor Cells
Laser Doppler Imaging

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Scleroderma, Limited
Sclerosis
Raynaud Disease
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Citric Acid
Sildenafil Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents

ClinicalTrials.gov processed this record on December 09, 2016