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

Study Overview
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Brief Summary
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The purpose of this study is determine if high-dose vitamin D supplementation improves clinical outcomes related to lung function and immunity in patients with Cystic Fibrosis who are admitted to the hospital with an acute lung infection.

Detailed Description
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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.

Official Title
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Vitamin D for Enhancing the Immune System in Cystic Fibrosis

Conditions
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Cystic Fibrosis, Respiratory Tract Infections

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholecalciferol (Vitamin D3)<br>Patients will be given 250,000 IU cholecalciferol in one bolus oral dose while they are in the hospital. Three months after the initial bolus dose, patients will take 50,000 IU oral cholecalciferol every other week for 9 months. | Dietary Supplement: Cholecalciferol<br>* Bolus dose of 250,000 IU during hospitalization + maintenance dose of 50,000 IU vitamin D every other week to be initiated 3 months after bolus dose<br>* Other names: Vitamin D;|
| No Intervention: Placebo<br>Patients will be given placebo pills in one bolus oral dose while they are in the hospital. Three months after the initial bolus dose, patients will take a placebo pill every other week for 9 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study enrollment to next pulmonary exacerbation requiring any antibiotics, hospitalization or death. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammation | We will examine whether the high-dose vitamin D treatment regimen decreases the pro-inflammatory cytokines, IL-6, IL-8, and TNF- α. | 12 months | 
| mortality as a separate outcome |  | 12 months | 
| re-hospitalization as a separate outcome |  | 12 months | 
| anti-microbial proteins | We will examine whether the high-dose vitamin D treatment regimen increases cathelicidin and hBD-2 mRNA expression in both peripheral blood mononuclear cells (PBMCs) and induced sputum (by quantitative PCR). | 12 months | 
| Lung function | We will examine whether high dose vitamin D improves serial lung function, as measured by FEV1 | 12 months | 
| Antibiotic use | Rates of pulmonary exacerbation requiring antibiotics due to presumed infection after 12 month | 12 months | 
| glucose metabolism | Rates of new onset diabetes and mean glucose values in each group | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, cholecalciferol, cystic fibrosis, respiratory tract infection, immunity, intervention studies, inflammation, dietary supplements, alpha-Defensins, Cytokines, mortality, biological markers, Biomedical Research