Use of monomeric and oligomeric flavanols in the dietary management of patients with type 2 diabetes mellitus and microalbuminuria (FLAVA trial): study protocol for a randomized controlled trial

Background: Patients with type 2 diabetes mellitus (T2D) are prone to micro-and macro-vascular complications. Monomeric and oligomeric flavanols (MOF) isolated from grape seeds (Vitis vinifera) have been linked to improved endothelial function and vascular health. The aim of this study is to determine the effect of a daily supplementation of 200 mg MOF on renal endothelial function of patients with T2D and microalbuminuria. Methods/design: For this double-blind, placebo-controlled, randomized, multicenter trial 96 individuals (ages 4085 years) with T2D and microalbuminuria will be recruited. Participants will be randomly assigned to the intervention group, receiving 200 mg of MOF daily for 3 months, or to the control group, receiving a placebo. The primary endpoint is the evolution over time in albumin excretion rate (AER) until 3 months of intervention as compared with placebo. Secondary endpoints are the evolution over time in established plasma markers of renal endothelial function-asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and von Willebrand Factor (vWF)-until 3 months of intervention as compared with placebo. Mixed modeling will be applied for the statistical analysis of the data. Discussion: We hypothesize that T2D patients with microalbuminuria have a medically determined requirement for MOF and that fulfilling this requirement will result in a decrease in AER and related endothelial biomarkers. If confirmed, this may lead to new insights in the dietary management of patients with T2D.