Scleroderma, Systemic, Scleroderma, Diffuse, Scleroderma, Limited, Raynaud Phenomenon
Conditions
Keywords
Sildenafil, Endothelial Progenitor Cells, Laser Doppler Imaging
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.
Interventions
DRUGSildenafil citrate
Oral sildenafil citratre, 50mg b.i.d., 8 weeks
Placebo pills similar to sildenafil citrate pills, b.i.d for 8 weeks
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus | 8 weeks | 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. | 8 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Frequency of Raynaud's Phenomenon Attacks | 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. |
Countries
Brazil
Participant flow
Recruitment details
Patients recruited at the Outpatient Clinic of The Federal University of Sao Paulo, between August 2011 and November 2012
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Citrate Oral Sildenafil citrate, 50mg, b.i.d.
Sildenafil citrate: Oral sildenafil citratre, 50mg b.i.d., 8 weeks | 21 |
| Sugar Pill Placebo: Placebo pills similar to sildenafil citrate pills, b.i.d for 8 weeks | 20 |
| Total | 41 |
Baseline characteristics
| Characteristic | Sildenafil Citrate | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 10.9 | 41.6 years STANDARD_DEVIATION 13.3 | 44.5 years STANDARD_DEVIATION 12.3 |
| Daily frequency of Raynuad's Phenomenon attacks | 2.3 number of attacks per day STANDARD_DEVIATION 2.5 | 1.9 number of attacks per day STANDARD_DEVIATION 2 | 2.1 number of attacks per day STANDARD_DEVIATION 2.3 |
| Digital skin microvascular blood flow measured by Laser Doppler Imaging (LDI) after cold stimulus. | 178.8 perfusion units STANDARD_DEVIATION 92.4 | 218.6 perfusion units STANDARD_DEVIATION 98.9 | 200.2 perfusion units STANDARD_DEVIATION 96.1 |
| Digital skin microvascular blood flow measured by Laser Doppler Imaging (LDI) before cold stimulus | 213.1 perfusion units STANDARD_DEVIATION 87.9 | 241.9 perfusion units STANDARD_DEVIATION 104.4 | 234.6 perfusion units STANDARD_DEVIATION 105.8 |
| Region of Enrollment Brazil | 21 participants | 20 participants | 41 participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 21 | 1 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 |
Outcome results
Primary
Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil Citrate | Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus. | 257.7 perfusion units | Standard Deviation 123.3 |
| Sugar Pill | Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) After Cold Stimulus. | 220.5 perfusion units | Standard Deviation 119.9 |
Primary
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.).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil Citrate | Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus | 260.0 perfusion units | Standard Deviation 108 |
| Sugar Pill | Digital Skin Microvascular Blood Flow Measured by Laser Doppler Imaging (LDI) Before Cold Stimulus | 246.3 perfusion units | Standard Deviation 122.6 |
Secondary
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil Citrate | Daily Frequency of Raynaud's Phenomenon Attacks | 1.9 number of attacks per day | Standard Deviation 2.4 |
| Sugar Pill | Daily Frequency of Raynaud's Phenomenon Attacks | 1.7 number of attacks per day | Standard Deviation 2.2 |