Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial

Abstract

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Background: </u> Vitamin D insufficiency is common in cystic fibrosis (CF) and vitamin D repletion may have an important role in improving clinical outcomes in CF. This randomized, placebo-controlled, pilot study examined the feasibility and impact of a single, large dose of cholecalciferol on vitamin D status and clinical outcomes in subjects with CF. <u>

Methods: </u> Thirty adults with were randomized in a double-blinded, pilot study to receive 250,000 IU cholecalciferol or placebo within 48 h of hospital admission for a pulmonary exacerbation. Concentrations of 25-hydroxyvitamin D (25(OH)D), clinical outcomes and potential adverse events were assessed up to one year after randomization. Mixed effects linear regression models were used to evaluate the difference in mean serum concentrations and log-rank analyses were used to evaluate survival. <u>

Results: </u> Data from all subjects was analyzed. Serum 25(OH)D concentrations increased from a mean of 30.6 ± 3.2 ng/mL to 58.1 ± 3.5 ng/mL (p < 0.001) at one week and 36.7 ± 2.6 ng/mL by 12 weeks (p = 0.06) in the vitamin D group; in contrast, serum 25(OH)D concentrations remained unchanged in the placebo group. Unadjusted, one-year survival and hospital-free days were increased in the vitamin D group (p = 0.029, p = 0.036; respectively). There was also a trend toward increased IV antibiotic therapy-free days in the vitamin D group (p = 0.073). There were no signs of hypervitaminosis D or adverse events. Serum PTH and calcium concentrations were similar across both groups. <u>

Conclusions: </u> In this pilot study, a single, oral bolus of cholecalciferol increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation. Further investigation is needed into the clinical impact of improved vitamin D status in patients with CF.

Keywords: anti-microbial peptide; cystic fibrosis; parathyroid hormone; pulmonary exacerbation; vitamin D.

Figure 2. Survival analysis by treatment group. The dashed line (vitamin D group) and solid line (placebo group) represent the unadjusted survival curves of adult CF patients (n = 30) randomized to either a single, oral 250,000 IU dose of cholecalciferol or identically matched placebo. Mortality was determined by CF clinic records over the following 12 mo. Subjects receiving cholecalciferol had a significantly increased survival over placebo (Log-rank analysis, p = 0.029). When adjusted for age and FEV_1% of predicted, there continued to be a trend for increased survival in the vitamin D group (Log-rank analysis, p = 0.09).

Figure 3. Recruitment and allocation of subjects. Subjects were recruited from the Emory Adult CF Center within 48 h of admission to the Emory University Hospital for the treatment of an acute pulmonary exacerbation. A total of 34 subjects were assessed for eligibility, 4 were ineligible and 30 subjects were block randomized to either 250,000 IU vitamin D₃ or placebo. All subject deaths were related to complications of cystic fibrosis. All patients were followed for 1-y or until death and data from all patients was analyzed for this study.

Figure 1. Unadjusted, mean change in 25-hydroxyvitamin D in response to a bolus dose of 250,000 IU of vitamin D₃ or placebo. The dashed line (vitamin D group) and solid line (placebo group) represent the unadjusted mean change in serum 25-hydroxyvitamin D concentrations [25(OH)D] at baseline, 1 week and 12 weeks in adult CF subjects randomized to either a single 250,000 IU dose of cholecalciferol or placebo. The change in mean serum 25(OH)D from baseline in the vitamin D group was +27.5 (± 13) ng/mL and +6.2 (± 11) ng/mL at week 1 and 12, respectively; contrasted to the change from baseline in the placebo group of -0.2 (± 13) ng/mL and -0.6 (± 14) ng/mL at week 1 and 12, respectively. (Mean with standard error bars, comparison between groups of the change from baseline at week 1, p < 0.001; at week 12, p = 0.06, Student’s t-test).