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

Early Phase 1

• Conditions: Systemic Sclerosis; Raynaud Phenomena
• Interventions: Drug: Methylprednisolone; Other: sodium chloride

• Registration Number: NCT03059979
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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

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

Study Timeline

• Study Start: 2017-01
• Study First Submitted: 2017-01-25
• Study First Submitted QC: 2017-02-16
• Study First Posted: 2017-02-23
• Status Verified: 2019-09
• Last Update Submitted: 2019-11-27
• Last Update Posted: 2019-11-29
• Primary Completion: 2021-07-01
• Study Completion: 2021-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methylprednisolone 1000 mg	Methylprednisolone	the methylprednisolone is dissolved in 100 cc of sodium chloride (NaCl 0.9%) by intravenous infusion in 30 minutes on three consecutive days
sodium chloride	sodium chloride	The placebo intervention with physiologic salt solution is identical in appearance

Primary Outcome Measures

Name	Time	Method
the change in capillary density from baseline	12 weeks	presence of enlarged and giant capillaries, hemorrhages, loss of capillaries, disorganization of the micro vascular array, and capillary ramifications.

Secondary Outcome Measures

Name	Time	Method
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
presence of synovitis from baseline	1 year
presence of tendon friction rubs from baseline	1 year
change in selected biomarkers: the interferon signature in peripheral blood from baseline	1 year	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
change in nail fold capillary changes other than capillary density and giant capillaries from baseline	1 year	changes in nail fold capillary pattern (early, active, late, normal
change in modified Rodnan skin score (mRSS) from baseline	1 year
presence of puffy fingers 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
general health 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
Change in 36-Item Short Form Survey (SF-36) total score from baseline	1 year

Trial Locations

Locations (1)

Radboudumc, Rheumatology department; 🇳🇱 Nijmegen, Gelderland, Netherlands