Cholecalciferol Supplementation in Strengthening Inspiratory Muscles in Cholecalciferol-Deficient Patients With Chronic Obstructive Pulmonary Disease

PRIMARY OBJECTIVES:

I. To establish the effect of D vitamin (vitamin D3) supplementation on inspiratory muscle
strength in vitamin D3-deficient chronic obstructive pulmonary disease (COPD) patients.
(Roswell Park Cancer Institute [RPCI]/University at Buffalo [UB] study) II. To establish the
12 month conversion rate. (University of Pittsburgh Cancer Institute [UPCI] study)

SECONDARY OBJECTIVES:

I. To establish the effect of vitamin D3 supplementation on peripheral muscle strength and
exercise capacity in vitamin D3-deficient COPD patients. (RPCI/UB study) II. To establish
the 3 and 6-month conversion rates. (UPCI study) III. To examine whether vitamin D3
supplementation is equally effective in COPD patients who are current versus former smokers.
(UPCI study)

TERTIARY OBJECTIVES:

I. To explore the effects of vitamin D3 supplementation in COPD patients on biomarkers of
lung cancer risk, inflammation, and pulmonary function. (UPCI study)

OUTLINE: Patients are randomized to 1 of 2 arms.

CONTROL ARM: Patients receive a placebo and multivitamin orally (PO) once daily (QD) for 52
weeks.

SUPPLEMENTATION ARM: Patients receive a multivitamin and cholecalciferol supplement PO QD
for 52 weeks.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Current or ex-smoker with at least a 10-year pack history

- COPD, defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity
(FVC) < 70% and FEV1% predicted < 80%

- 25-hydroxy vitamin D3 (25[OH]D3) level less than 20 ng/mL prior to study initiation

- Willingness to comply with study guidelines

- Willingness to avoid alternative/additional vitamin D3 supplementation for the
duration of the trial

- Subject must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure

Exclusion Criteria:

- Personal history of lung cancer or head and neck cancer

- History of malabsorption syndrome (e.g., pancreatic insufficiency, celiac disease, or
tropical sprue)

- History of known thyroid disease

- History of known sarcoid disease

- History of known abnormalities in calcium metabolism

- Hypercalcemia (serum calcium in excess of laboratory upper limit normal [ULN])

- Self-reported consumption of more than 4 alcoholic drinks per day

- Use of anti-seizure medications phenobarbital or phenytoin, which can disrupt vitamin
D metabolism

- History of known renal dysfunction

- History of known nephrolithiasis (kidney stones)

- Current use of supplemental oxygen

- Inability to exercise due to musculoskeletal issue, osteoarthritis or underlying
cardiac disease

- Current participation in a cancer intervention prevention study, except for smoking
cessation

- Any condition which in the Investigator's opinion deems the subject an unsuitable
candidate to receive study drug

- Inability to swallow pills

- Vitamin D supplementation > 2,000 IU/day of vitamin D within 30 days prior to
enrollment

- Positive Pregnancy Test