Cathelicidin and Vitamin D: Impact on Populations At-Risk and With COPD

Phase 2

Completed

Brief Summary: This proposal will evaluate a potential mechanism of increased risk of lung function impairment, cathelicidin levels, as well as determine if vitamin D replacement can alter this pathway. This study will improve the understanding of factors which can lead to chronic lung disease. If effective, this application would also provide the justification to study vitamin D as a therapy to improve lung health.

Detailed Description: Understanding mechanisms leading to decrements in lung function, the physiologic hallmark of obstructive lung diseases including chronic obstructive pulmonary disease (COPD), are necessary to inform interventions to improve lung health. The antimicrobial peptide cathelicidin, and its primary regulator vitamin D, has been implicated in development and progression of chronic lung disease. In this study, the investigators will evaluate the effect of oral vitamin D supplementation on lung cathelicidin levels in humans. Cathelicidin has bactericidal and inflammatory activities in the lung and is regulated by vitamin D levels. The investigators hypothesize that oral vitamin D supplementation will raise cathelicidin levels in the pulmonary compartment, thereby restoring lung cathelicidin deficiency. To test this hypothesis, the investigators will recruit from two ongoing cohort studies: 1) At Johns Hopkins, the Subpopulations and Intermediate Outcome Measures in COPD Study study and 2)at University of North Carolina at Chapel Hill pulmonary and general medicine clinic. The investigators will measure blood and lung lavage cathelicidin levels in 40 vitamin D insufficient individuals (20 from each cohort) before and after eight weeks of oral vitamin D supplementation to determine the effect of vitamin D supplementation on cathelicidin levels.

Recruitment & Eligibility

Inclusion Criteria

Men and women age 18-65 who are current or former smokers
Serum calcium<10.5mg/dL
25-Hydroxy Vitamin D (OHD)<20 ng/mL
Creatinine Clearance ≥60 mL/min as estimated by the Cockcroft-Gault equation
Women of reproductive potential with negative serum or urine pregnancy test and subjects must refrain from participating in a conception process and subject/partner must use at least 2 reliable forms of contraceptives for the duration of the study
For participants with COPD, Forced Expiratory Volume in 1 second (FEV1) greater than 50% predicted.
For smokers, current cigarette use (defined as regularly smoking 5 cigarettes per day)

Exclusion Criteria

Current use of vitamin D supplements
Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations
Pregnancy or currently breast-feeding
History of nephrolithiasis
HIV positive serostatus
Continuous oxygen use >2 liters/min via nasal cannula
Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.

Arm && Interventions

Group	Intervention	Description
Vitamin D3	Vitamin D3	Oral supplementation with 50,000 IU vitamin D3 weekly for eight weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Lung Cathelicidin Level at 8 Weeks	Baseline and 8 weeks	Change from baseline to 8 weeks in bronchoscopic lavage lung cathelicidin levels after vitamin D supplementation (comparison between pre- and post-supplementation cathelicidin levels using paired t-tests for repeated measures)

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Blood Cathelicidin at 8 Weeks	Baseline and 8 weeks	Change from baseline to 8 weeks in blood cathelicidin levels after vitamin D supplementation (comparison between pre- and post-supplementation cathelicidin levels using paired t-tests for repeated measures)
Change From Baseline in Blood Vitamin D Binding Protein at 8 Weeks	Baseline and 8 weeks	Change from baseline to 8 weeks in blood vitamin D binding protein after vitamin D supplementation (comparison between pre- and post-supplementation cathelicidin levels using paired t-tests for repeated measures)

Locations (2): Meadowmont Pulmonary Research Clinic
🇺🇸
Chapel Hill, North Carolina, United States
Johns Hopkins Clinical Research Unit
🇺🇸
Baltimore, Maryland, United States