Efficiency and safety of transcranial direct current stimulation in the treatment of fatigue in patients with Primary Systemic Vasculitis: clinical trial, randomized, double-blind and sham-controlled

Abstract

Systemic Primary Vasculitis (SPV) refers to rare and heterogeneous diseases that present with blood vessel inflammation as their main feature. In addition, because of these diseases' chronic systemic manifestation, drug treatment, and/or comorbidities, patients with SPV have reductions in their quality of life, functional capability, aerobic capacity, and performance of activities of daily living. All of these factors are part of a vicious cycle in which they are enhanced by the high prevalence of fatigue in these patients. Several studies have shown that similar to physical exercises, using transcranial Direct Current Stimulation (tDCS) is effective for decreasing fatigue and, consequently, improving patients' functional capacity and quality of life. tDCS is a noninvasive brain stimulation technique that entails applying low-intensity continuous electric current over the intact scalp and in the area of cerebral interest, allowing the modulation of cortical excitability and the induction of neuroplasticity. In addition, the combination of tDCS and physical exercises can enhance the reduction of fatigue through a neuroplasticity mechanism, enhancing the connectivity of the central and peripheral neural networks and increasing success in improving patients' quality of life. tDCS has been used extensively in the treatment of several diseases, but not systemic autoimmune diseases. In this context, our group has been a pioneer in the application of tDCS in patients with systemic autoimmune myopathies. Our results have shown that in addition to being safe, tDCS is effective for improving these patients' quality of life. Therefore, the aim of the present study is to expand our research by evaluating the safety and effects of tDCS [associated with Aerobic Training (AT)] in patients with SPV (specifically Takayasu's Arteritis [TAK] and Granulomatosis with Polyangiitis [GPA]). For this purpose, 54 patients with TAK and 28 patients with GPA will be selected and subsequently randomized in a 1:1 ratio and stratified by disease, thus establishing the groups TAK (Sham and tDCS) and GPA (Sham and tDCS). Additionally, we will pair a healthy control group by sex, age, and body mass index to carry out a cross-sectional analysis (phase 1), comparing patients (TAK and GPA) with respect to fatigue, quality of life, functional capacity, pain, sleep quality, aerobic capacity, serum lactate, comorbidities, and disease status. Longitudinally (phase 2), we will carry out a randomized, double-blind, controlled sham clinical study encompassing four weeks (11 sessions) of intervention. In addition to previous assessments and a four-month follow-up (counting from the end of the protocol), participants' fatigue, quality of life, aerobic and functional capacity, subjective perception of effort, subjective perception of recovery, and serum lactate (to assess training intensity) will be evaluated. The safety of tDCS also will be assessed with regard to reactivation of the disease and any adverse effects of its application. The expected effect is a reduction in patients' degree of fatigue, contributing to clinical improvement, reduced use of medications, and ultimately, a greater quality of life. In addition, this study could broaden the understanding of the importance of cortical plasticity in classic symptoms of SPV, providing a new therapeutic tool for application in clinical practice. (AU)