Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial

Abstract

Introduction Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. Methods and analysis The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. Primary objective: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). Secondary objectives: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. Ethics and dissemination This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings. Trial registration number NCT02548364; Pre-results.

Structural diversification of vitamin D using microbial biotransformations

“…The cardiovascular system also reaps the benefits of vitamin D, with studies indicating a potential reduction in risks associated with hypertension, coronary artery disease, and heart failure (de la Guía-Galipienso et al 2021 ; Latic and Erben 2020 ). More specifically, low plasma levels of vitamin D are associated with vascular damage and also play an important role in myocardial status (Assalin et al 2013 ; Tuñón et al 2016 ). Although the negative association between vitamin D deficiency and cardiovascular disease has been described in a multitude of studies in animal models, clinical trials have failed to demonstrate the benefit of vitamin D supplementation on cardiovascular health (Tuñón et al 2016 ).…”

“…More specifically, low plasma levels of vitamin D are associated with vascular damage and also play an important role in myocardial status (Assalin et al 2013 ; Tuñón et al 2016 ). Although the negative association between vitamin D deficiency and cardiovascular disease has been described in a multitude of studies in animal models, clinical trials have failed to demonstrate the benefit of vitamin D supplementation on cardiovascular health (Tuñón et al 2016 ). Additionally, there is an inverse relationship between vitamin D and the risk of developing type 2 diabetes, as it appears to enhance insulin sensitivity (Lips et al 2017 ).…”

Vitamina D e fatores de risco para doença cardiovascular em crianças e adolescentes

“…Os estudos foram submetidos a análise metododológica através do checklist de JADAD (1997) 15 (Quadro 1) sendo que os artigos selecionados tinham escore 5 (máximo), demonstrando que todos os estudos descreveram uma metodologia adequada de acordo com o instrumento de avaliação. no endotélio e nas células do miocárdio 24 , já tendo sido relatados em estudos em adultos, especificamente em mulheres com deficiência de vitamina D, que apresentavam alto risco cardiovascular 16 . Há também um estudo multicêntrico, randomizado, em andamento, que pretende avaliar a função do ventrículo esquerdo e os marcadores inflamatórios em adultos submetidos à angioplastia primária e o uso de vitamina D 18 .…”