The Evaluation of Vitiligous lesions Repigmentation after the Administration of Atorvastatin calcium salt and Simvastatin-acid sodium salt in patients with active vitiligo (EVRAAS), a pilot study: study protocol for a randomized controlled trial

Abstract

BackgroundVitiligo is a chronic skin disorder presenting with depigmentation, the pathogenesis of which is complex but the autoimmune theory is now preferred. Multiple immunologic processes, including stimulation of the T-helper (Th)1 response, formation of autoreactive melanocyte-specific CD8+ T lymphocytes, a decrease in the blood concentration of T regulatory (Treg) cells, and an increase in interleukin (IL)-17 and interferon (IFN) concentration, have been shown to contribute to vitiligo progression and maintenance. The aim of this study is to evaluate the influence of simvastatin and atorvastatin on vitiligous lesions in patients with nonsegmental vitiligo (NSV). According to available data, statins act through several immunological pathways, potentially reversing undesirable phenomena underlying autoimmune vitiligo pathogenesis.Methods/designA study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of at least 24 active NSV patients presenting with vitiligous lesions on both upper and lower limbs. The clinical effects of ointments containing 1% simvastatin-acid sodium salt or 1% atorvastatin calcium salt applied on a preselected limb will be assessed in comparison with vehicle ointment applied on the opposite limb. All study participants will undergo clinical evaluation using body surface area (BSA) and Vitiligo Area Scoring Index (VASI) scales at baseline and at weeks 4, 8, and 12 time points. A precise assessment of skin lesions will be performed using photographic documentation obtained during each study visit and processed with NIS-Elements software.DiscussionCurrently available vitiligo topical therapeutic approaches including calcineurin inhibitors and corticosteroids remain poorly effective and are associated with either relatively high cost or potentially dangerous adverse effects. The clinical application of orally administrated statins, widely used as systemic cholesterol-lowering agents, in vitiligous patients has only been tested in two clinical trials; however, data on their potential usefulness is scarce. Moreover, due to a high risk of clinically significant toxicity, topical administration was recommended by researchers. This study is the first to evaluate safety and efficacy of the topical use of statins in patients presenting with NSV.Trial registrationClinicaltrials.gov, NCT03247400. Registered on 05 August 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3168-4) contains supplementary material, which is available to authorized users.

Vitiligo: The Association With Metabolic Syndrome and the Role of Simvastatin as an Immunomodulator

“…Simvastatin, a potent statin drug used widely in dyslipidemia and cardiovascular diseases, also possesses antioxidant and anti-inflammatory properties by its action on CD8+ T cells. It inhibits the production of proinflammatory cytokines, which is an important factor in the pathogenesis of vitiligo, as discussed above [10].…”

“…Simvastatin, a potent statin drug used widely in dyslipidemia and cardiovascular diseases, also possesses antioxidant and anti-inflammatory properties by its action on CD8+ T cells. It inhibits the production of pro-inflammatory cytokines, which is an important factor in the pathogenesis of vitiligo, as discussed above [ 10 ]. A small clinical trial conducted by Vanderweil et al found topical simvastatin to be more useful than the systemic form, citing potential adverse effects of the systemic form [ 33 ].…”

“…Simvastatin, by inhibition of HMG-CoA reductase, helps prevent the generation of isoprenoids [ 9 ]. In addition, it directly inhibits CD8+ T-cells specific to melanocytes, which leads to limited proliferation and decreased interferon gamma (IFN-γ) production [ 10 ]. We will further try to analyze whether simvastatin can be used as an immunomodulating agent in vitiligo.…”

Simvastatin in vitiligo: an update with recent review of the literature

“…With growing safety concerns regarding systemic simvastatin, a pilot randomized controlled trial is currently underway involving active vitiligo patients and topical atorvastatin calcium salt (1%) or simvastatin‐acid sodium salt (1%) over 12 weeks (Vitiligous lesions Repigmentation after the Administration of Atorvastatin calcium salt and simvastatin‐acid sodium salt in patients with active vitiligo [EVRAAS] trial). Currently, patients are being recruited for this study 39 …”

Near‐infrared spectroscopy as a potential non‐invasive tool in the assessment of disease activity in vitiligo patients

“…[ 3 ] In patients with an active form, skin and blood is abundant with melanocyte‐specific, autoreactive CD8 + T cells which have an important role in depigmentation. [ 4 ] However, previous research has also shown a marked redox imbalance in keratinocytes obtained from the perilesional skin of patients with active disease (eg increase in reactive oxygen species production and lipoperoxidation). [ 5,6 ] One of the obstacles in the clinical management of vitiligo is the assessment of disease activity.…”