Efficacy and Safety of High-Dose Vitamin D Supplementation Combined with an Enuresis Alarm vs Alarm Alone in Children with Primary Monosymptomatic Nocturnal Enuresis: A Randomized Clinical Trial.

Abstract

This study evaluated the efficacy and safety of high-dose vitamin D supplementation (VDS) combined with enuresis alarm (EA) therapy in children with primary monosymptomatic nocturnal enuresis (PMNE). A two-arm randomized clinical trial was conducted at a tertiary center in China between December 2024 and May 2025. Children with PMNE and serum 25-hydroxyvitamin D (25(OH)D) levels below 30 ng/mL were randomly assigned to receive either 8 weeks of VDS (vitamin D3 soft capsules, 2400 IU/day) plus EA (VDS + EA group) or EA (EA group). The primary outcome was treatment response. Secondary outcomes included change in weekly frequency of wet nights, quality-of-life (QoL) scores and treatment satisfaction. Safety was assessed by recording treatment-emergent adverse events (TEAEs). A total of 304 children were enrolled, of whom 262 (130 in the VDS + EA group and 132 in the EA group) were included in the final analysis. Compared with the EA group, the VDS + EA group showed higher response rates (RR 1.22; 95% CI 1.01-1.49; <i>P</i> = 0.04), complete response rates (RR 1.54; 95% CI 1.10-2.15; <i>P</i> = 0.01), a greater reduction in weekly wet nights (median difference, 1; 95% CI, 0-2; <i>P</i> = 0.003), and greater improvements in QoL and treatment satisfaction. No statistically significant difference in the risk of TEAEs was observed between groups. High-dose VDS combined with EA was effective and well tolerated for treating PMNE in children, supporting its potential as a promising therapeutic approach.