A randomized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes

Abstract

Background & aims: This participant-blinded parallel-group randomized placebo-controlled study demonstrated that alfacalcidol (vitamin D analogue) preserves beta cell function in newly diagnosed type 1 diabetes (T1DM) in children.

Methods: Subjects from outpatient clinic were randomized to intervention and control groups. Inclusion: (1) age 8-15, (2) T1DM, (3) duration <8 weeks, (4) no chronic diseases, (5) stable diet. Exclusion: (1) vitamin D, calcium supplements or fortified foods, (2) hypercalcemia. Intervention group received alfacalcidol 0.25 μg twice daily, while control group received placebo. Insulin given physician-titrated to blood glucose. Safety monitored by serum calcium and phosphate. Beta cell function assessed at 0, 3, 6 months using fasting C-peptide (FCP) and daily insulin dosage per body weight (DID). Primary outcome measured using multivariate repeated measures GLM-ANOVA, with FCP and DID as primary measures and age, gender, sunlight exposure, 25-hydroxy vitamin D, and HbA1c as covariates.

Results: Of 61 subjects, 7 dropped out. GLM-ANOVA showed that groups were different (p=0.019, Eta-squared=0.087), with no significant covariates. FCP was higher and DID lower in the intervention group, with males having stronger responses to alfacalcidol (p=0.001). No adverse effects were observed.

Conclusions: The study confirmed that alfacalcidol can safely preserve beta cell function in newly diagnosed T1DM in children, with a stronger effect in males.

Clinical trial reg no: IRCT201205159753N1.

Keywords: 1-alpha-hydroxycholecalciferol; Alfacalcidol; C-Peptide; DID; Diabetes mellitus; FCP; GLM-ANOVA; HLA; HbA1c; Hydroxycholecalciferols; Insulin-secreting cells; Iran; Randomized controlled trial; SMBG; T1DM; Type 1; VDR; daily insulin dosage per body weight; fasting C-peptide; glycated hemoglobin; human leukocyte antigen; multivariate general linear modeling repeated measures ANOVA; self-monitored blood glucose; type 1 diabetes; vitamin D receptor.