Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Cathelicidin, Vitamin D
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.
Interventions
DRUGVitamin D3
Oral supplementation with 50,000 IU vitamin D3 weekly for eight weeks in individuals with reduced vitamin D levels.
Sponsors
Johns Hopkins University
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment: 11/10/2015-11/15/2018
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3 Oral supplementation with 50,000 IU vitamin D3 weekly for eight weeks
Vitamin D3: Oral supplementation with 50,000 IU vitamin D3 weekly for eight weeks in individuals with reduced vitamin D levels. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
Baseline characteristics
| Characteristic | Vitamin D3 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 52.8 years STANDARD_DEVIATION 11.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 23 |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 1 / 23 |
Outcome results
Primary
Change From Baseline in Lung Cathelicidin Level at 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)
Time frame: Baseline and 8 weeks
Population: Analysis population represents N=17 participants who completed all study procedures
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitamin D3 | Change From Baseline in Lung Cathelicidin Level at 8 Weeks | -65.5 pg/mL |
p-value: 0.2195% CI: [-172.4, 41.3]t-test, 2 sided
Secondary
Change From Baseline in Blood Cathelicidin at 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)
Time frame: Baseline and 8 weeks
Population: Analysis population represents N=17 participants who completed all study procedures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 | Change From Baseline in Blood Cathelicidin at 8 Weeks | -0.55 ng/ml | Standard Deviation 12.6 |
p-value: 0.8695% CI: [-7.02, 5.91]t-test, 2 sided
Secondary
Change From Baseline in Blood Vitamin D Binding Protein at 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)
Time frame: Baseline and 8 weeks
Population: The outcome measure of Vitamin D Binding Protein was not collected nor assessed on any study participants. This was due to technical limitations related to the assay.