Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial

Abstract

Background: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF.

Objectives: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations.

Methods: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%).

Results: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin.

Conclusions: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

Keywords: cathelicidin; clinical trial; cystic fibrosis; lung function; nutrition; pulmonary exacerbation; vitamin D.

© 2019 American Society for Nutrition.

Figures

FIGURE 1

CONSORT study diagram for the vitamin D for the Immune System (DISC) Study: a multicenter, double-blind, randomized, placebo-controlled trial. CONSORT, Consolidated Standards of Reporting Trials; UAB, The University of Alabama at Birmingham.

FIGURE 2

Time to first composite event (death or pulmonary exacerbation) by treatment group in the vitamin D for the Immune System (DISC) Study. The Kaplan–Meier curve for the time to first composite event by vitamin D (dotted line) and placebo (solid line) group is displayed. There were no differences in time to first composite event in the vitamin D and placebo groups in adults with cystic fibrosis followed for 1 y as assessed by Cox proportional hazards regression (95% CI: 0.54, 1.34, P = 0.48).

FIGURE 3

Markers of lung function, calcium status, and antimicrobial peptide concentrations in adult subjects randomly assigned to vitamin D or placebo by study visit up to 1 y. Secondary endpoints in subjects randomly assigned to vitamin D (dotted line) and placebo (solid line) were measured at baseline and 1, 3, 6, and 12 mo after random assignment. Mixed-effects analyses did not reveal any differences between the 2 groups in the 6 measures: FEV1% predicted (marker of lung function), total serum calcium, serum albumin, serum creatinine, LL-37, or return to baseline lung function (%). Each point on the plot is the estimated group mean at that time point, and the vertical bars correspond to 1 SD. The sample size at each time point is reported near the error bar. FEV1%, percentage of predicted forced expiratory volume in 1 s; LL-37, cathelicidin; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 4

Mean 25-hydroxyvitamin D concentrations in the vitamin D and placebo groups. Serum 25(OH)D concentrations in the group randomly assigned to vitamin D (dotted line) were significantly higher than in the placebo group (solid line) at days 1–7 and at 1, 6, and 12 mo in a mixed-effects regression analysis. Each point on the plot is the estimated group mean at that time point, and the vertical bars correspond to 1 SD. The sample size at each time point is reported near the error bar. 25(OH)D, 25-hydroxyvitamin D.