Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: a phase one open-label study

BACKGROUND: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH)(2) vitamin D(3) of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D(3) supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. METHODS: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D(3) (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus- specific IgE, vitamin D levels, FEV(1), urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. RESULTS: Six months of vitamin D(3) supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). CONCLUSIONS: 4000 IU vitamin D(3) daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. . Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. . CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov as NCT01222273.