The Effect of High Dose Methylprednisolone on Nailfold in Early Systemic Sclerosis ( SSc )

Study Overview
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Brief Summary
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This is a 12 week double-blind randomized placebo controlled trial in which 30 patients with very early SSc, fulfilling the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) criteria (9) will be randomized in a 2:1 fashion to receive intravenous methylprednisolone or placebo. Three-day treatment courses are given at week 0, week 4 and week 8. The final assessment is at week 12, and patients will be followed up to one year after baseline

Detailed Description
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Systemic sclerosis is a disease with a high burden caused by morbidity and increased mortality. To date a cure for SSc is not available. In this trial, patients are treated very early in the disease which could change the long term outcome of SSc in these patients. In daily practice, patients so early in the disease course are not treated although they might be at risk for early escalation and internal organ involvement, reducing their prognosis. A trial to investigate the efficacy of a relative save, inexpensive and easy accessible treatment will provide us with the opportunity to change the disease course and reducing the disease burden of a portion of the SSc patients

Official Title
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Hit Hard and Early. The Effect of High Dose Methylprednisolone on Nailfold Capillary Changes and Biomarkers in Early SSc: a 12-week Randomised Explorative Double-blind Placebo-controlled Trial.

Conditions
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Systemic Sclerosis, Raynaud Phenomena

Intervention / Treatment
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* Drug: Methylprednisolone
* Other: sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age over 18 years Fulfilling VEDOSS criteria (9): Raynauds' Phenomenon and Positive for disease specific auto antibodies (anti-centromere or anti-topoisomerase antibodies) and typical nail fold capillaroscopic findings Puffy fingers < 3 years Modified Rodnan skin score = 0 Exclusion Criteria: Presence of acroosclerosis, acrosteolysis and digital ulcers Presence of anti-RNA polymerase III auto antibodies Previous systemic treatment for SSc, namely: methotrexate, prednisone (> 14 days in previous 6 months), mofetil mycophenolate cyclophosphamide. Clinically significant internal organ involvement: diffusion capacity of lung for carbon monoxide (DLCO) < 80% predicted, vital capacity (VC) < 70% predicted renal dysfunction with glomerular filtration rate (GFR) < 60 ml/min diastolic dysfunction > grade 1 on echocardiography pulmonary hypertension weight loss >10% in the last 6 months with unknown cause Contra-indications for methylprednisolone, such as: pregnancy, lactation psychotic or depressive disorder ulcus duodeni or ventriculi untreated hypertension (> 160-90 mmHg) acute infections

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone 1000 mg<br>the methylprednisolone is dissolved in 100 cc of sodium chloride (NaCl 0.9%) by intravenous infusion in 30 minutes on three consecutive days | Drug: Methylprednisolone<br>* methylprednisolone 1000 mg dissolved in 100 cc of NaCl 0.9%, by intravenous infusion in 30 minutes on three consecutive days Three-day treatment courses are given at week 0, week 4 and week 8.<br>* Other names: Solu-Medrol;|
| Placebo Comparator: sodium chloride<br>The placebo intervention with physiologic salt solution is identical in appearance | Other: sodium chloride<br>* 100 cc of NaCl 0,9% , administered by intravenous infusion in 30 minutes on three consecutive days Three-day treatment courses are given at week 0, week 4 and week 8.<br>* Other names: NaCl 0,9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change in capillary density from baseline | presence of enlarged and giant capillaries, hemorrhages, loss of capillaries, disorganization of the micro vascular array, and capillary ramifications. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in selected biomarkers: the interferon signature in peripheral blood from baseline | Plasma biomarkers consist soluble inflammatory mediators platelet factor 4, interleukin-1β, interleukin-6, tumor necrosis factor-α, endothelin-1, intercellular adhesion molecule-1 and vascular endothelial growth factor | 1 year | 
| change in nail fold capillary changes other than capillary density and giant capillaries from baseline | changes in nail fold capillary pattern (early, active, late, normal | 1 year | 
| change in modified Rodnan skin score (mRSS) from baseline |  | 1 year | 
| presence of puffy fingers from baseline |  | 1 year | 
| presence of synovitis from baseline |  | 1 year | 
| presence of tendon friction rubs from baseline |  | 1 year | 
| fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline |  | 1 year | 
| pulmonary function tests from baseline |  | 1 year | 
| presence of interstitial lung disease from baseline |  | 1 year | 
| suspicion of pulmonary hypertension from baseline |  | 1 year | 
| Change in physical function from baseline |  | 1 year | 
| general health score from baseline |  | 1 year | 
| Change in 36-Item Short Form Survey (SF-36) total score from baseline |  | 1 year | 
| Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline |  | 1 year | 
| Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline |  | 1 year | 
| Change in gastrointestinal tract ( GIT ) total score from baseline |  | 1 year |