Journal Article

Hit hard and early: analysing the effects of high-dose methylprednisolone on nailfold capillary changes and biomarkers in very early systemic sclerosis: study protocol for a 12-week randomised controlled trial

van der Kraan, Peter M., Vonk, Madelon C., Kersten, Brigit E., Knaapen-Hans, Hanneke K. A., van den Hombergh, Wieneke M. T., van den Hoogen, Frank H. J., Fransen, Jaap, Thurlings, Rogier M.

2018

Overview

Background Mounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease. Therefore, patients with very early SSc could benefit from early treatments targeting inflammation. Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. Several studies have demonstrated a mixed response to treatment with glucocorticoids in SSc, probably because it is seldom initiated at very early stages of the disease. We hypothesise that by inhibiting the inflammatory process driving SSc disease progression, glucocorticoid treatments will induce remission in patients with very early SSc. Methods/design This study is a 12-week, randomised, double-blind, placebo-controlled trial analysing the effects of high-dose intravenous methylprednisolone in very early SSc. Thirty patients who fulfil the criteria for very early SSc will be randomly assigned in a 2:1 ratio to receive either intravenous methylprednisolone or a placebo on three consecutive days over three consecutive months. In this study, the primary endpoint will be the change in capillary density between the baseline and after 12 weeks of treatment. The secondary outcomes of this study are a change in selected biomarkers, other changes in the nailfold capillaries, signs of established SSc and changes in physical function, general health and utilities, as reported through questionnaires. Discussion This trial is the first aiming to treat very early SSc and is promising because it targets the very early stages of the disease process by using an inexpensive and relatively safe treatment known to be highly effective against inflammation. The use of vasculopathy and inflammatory biomarkers as well as clinical signs and symptoms as the endpoints in our study enables us to meet the patient need for markers of disease activity. If it is possible to prevent clinically significant disease in patients with very early SSc by using a safe treatment, this will cause a paradigm shift in scleroderma care and research. Trial registration ClinicalTrials.gov Identifier: NCT03059979 . Registered on 20 February 2017.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Administration, Intravenous / Anti-Inflammatory Agents - administration & dosage / Anti-Inflammatory Agents - adverse effects / Antibodies / Autoimmune diseases / Biomarkers / Biomarkers - blood / Biomedicine / Blood vessels / Capillaries - drug effects / Capillaries - pathology / Capillaries - physiopathology / Carbon monoxide / Care and treatment / Clinical Protocols / Cytokines / Development and progression / Disease / Double-Blind Method / Early Diagnosis / Glucocorticoids / Glucocorticoids - administration & dosage / Glucocorticoids - adverse effects / Health aspects / Health Sciences / Humans / Immune response / Inflammation / Inflammation Mediators - blood / Medical diagnosis / Medicine / Medicine & Public Health / Methylprednisolone / Methylprednisolone - administration & dosage / Methylprednisolone - adverse effects / Microscopic Angioscopy / Mortality / Nailfold capillaroscopy / Nails - blood supply / Netherlands / Patients / Predictive Value of Tests / Pulmonary hypertension / Questionnaires / Randomised controlled trial / Research Design / Rheumatology / RNA polymerase / Scleroderma / Scleroderma (Disease) / Scleroderma, Systemic - blood / Scleroderma, Systemic - drug therapy / Scleroderma, Systemic - pathology / Statistics for Life Sciences / Study Protocol / Systemic sclerosis / Testing / Time Factors / Treatment Outcome / Tumor necrosis factor-TNF / Vascular endothelial growth factor / Very early diagnosis of systemic sclerosis