Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC Study)

Patients with Cystic Fibrosis (CF) have a shorter life span than the general population due
to complications with lung infections, which eventually progress to lung failure. New
research has suggested that high levels of vitamin D may be protective against lung
infections and may promote the action of anti-bacterial proteins needed to ward off
infections. Research has also suggested that high vitamin D levels are linked to lower
mortality rates; however these hypotheses have not been adequately studied in patients with
CF. An investigation of the effects of vitamin D supplementation is of particular interest
in this population because patients with CF generally have high rates of vitamin D
deficiency. The investigators have preliminary data from a previous study suggesting that
vitamin D supplementation in patients with CF lowers markers of inflammation, promotes
anti-bacterial proteins, and reduces mortality. In this proposed multi-center study the
investigators will examine the effects of a high dose vitamin D supplementation on patients
with CF who are admitted to the hospital for lung infection. The investigators will use a
randomized, placebo-controlled trial design to determine if mortality and infection rates
over 1 year are reduced in patients who receive the high-dose vitamin D supplementation
compared to those who receive placebo. The investigators will also determine if vitamin D
affects markers of inflammation and anti-bacterial proteins, as well as CF-related clinical
outcomes, such as lung function. The investigators plan to recruit 280 adults and
adolescents with CF (ages > 16yrs), with approximately 150 subjects recruited at Emory
(Emory University Hospital and Children's Healthcare of Atlanta). Participants will
initially be seen by the study researchers during the first week of in-patient
hospitalization, and they will be followed over the course of one year during their
regularly-scheduled out-patient CF clinic visits. The treatment group will receive an
initial oral bolus dose of 250,000 IU vitamin D, and at 3 months follow-up they will receive
50,000 IU vitamin D every other week. Current CF Guidelines for vitamin D supplementation
recommend a daily intake of 800 IU of vitamin D per day, therefore in addition to the
vitamin D or placebo they receive at the beginning of the study and at 3 months, all
participants will receive 800 IU of vitamin D daily. If our hypotheses are correct, this
study has potential for reducing infection and promoting survival in patients with CF using
vitamin D, a relatively inexpensive supplement.

Inclusion Criteria:

- Adult and adolescent CF patients

- age >16 years

- admitted to the inpatient hospital setting for a pulmonary exacerbation of cystic
fibrosis

- enrolled within 72 hours of admission

- able to tolerate oral medications

- expected to survive hospitalization

Exclusion Criteria:

- Inability to obtain or declined informed consent from the subject and/or legally
authorized representative

- History of serum 25(OH)D >55 ng/mL in the past 12 months

- History of serum 25(OH)D <10 ng/mL in the past 12 months

- Current intake of more than 2,000 IU of vitamin D

- intake of 2,000 IU of vitamin D or its equivalent weekly dose (14,000 IU) for more
than 1 week at any time within the past 60 days or intake of greater than vitamin D
10,000 IU once at anytime in the past 60 days

- Pregnancy or plans to become pregnant during the course of the study (12 months)

- History of disorders associated with hypercalcemia including parathyroid disease

- Current hypercalcemia (albumin-corrected serum calcium >10.8 mg/dL or ionized calcium
>5.2 mg/dL)

- History of nephrolithiasis

- Chronic kidney disease worse than stage III (<60 ml/min)

- Oral or intravenous glucocorticoid use currently or in the past month

- History of lung transplantation or awaiting lung transplant

- patient in hospice care

- FEV1% predicted <20%

- Current significant hepatic dysfunction total bilirubin > 2.5 mg/dL with direct
bilirubin > 1.0 mg/dL

- Current use of cytotoxic or immunosuppressive drugs

- History of AIDS

- History of illicit drug abuse (defined as history of enrollment into a drug
rehabilitation program or hospital visits due to drug use within the past 3 years or
any use of the following drugs in the past 6 months (cocaine, opiates, amphetamines,
marijuana) or any positive toxicology screen for (cocaine, opiates, amphetamines,
marijuana)

- Previous enrollment in the study

- Current enrollment in another intervention trial

- Too ill to participate in study based on investigator's or study team's opinion