Materials and methods
This randomized, double-blind, placebo-controlled, investigator-initiated study was conducted according to the Dutch Act on Medical Research involving Human Subjects (WMO), and the study protocol was approved by the Medical Ethics Committee (Stichting Beoordeling Ethiek Biomedisch Onderzoek, Assen, The Netherlands) prior to the start of the clinical phase. The subjects provided written informed consent before any study-related procedures were undertaken.