Clinical trial NCT02877641: Cholecalciferol Supplementation in Strengthening Inspiratory Muscles in Cholecalciferol-Deficient Patients With Chronic Obstructive Pulmonary Disease
Official title: Effect of Once Daily Oral Vitamin D3 Supplementation on Inspiratory Muscle Strength in Vitamin D3-Deficient COPD Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Muscle Weakness
Keywords: Current Smoker
Former Smoker
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-08-24
Enrollment: 4
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This phase IIb randomized trial studies how well cholecalciferol (vitamin D3) supplementation works in strengthening inspiratory muscles in cholecalciferol-deficient patients with chronic obstructive pulmonary disease (COPD). Cholecalciferol supplementation may help reduce the risk of developing lung cancer and strengthen the diaphragm in cholecalciferol-deficient patients with COPD.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Conversion rate, defined as the proportion of patients whose baseline cholecalciferol deficiency is corrected (UPCI study)
timeFrame: At 12 months
measure: Inspiratory muscle strength assessed by respiratory capacity (RPCI/UB study)
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Change in exercise capacity assessed by respiratory exercise tests (RPCI/UB study)
timeFrame: Baseline to 24 weeks
measure: Change in peripheral muscle strength assessed by the elbow flexion test (RPCI/UB study)
timeFrame: Baseline to 24 weeks
measure: Conversion rate, defined as the proportion of patients whose baseline cholecalciferol deficiency is corrected (UPCI study)
timeFrame: At 3 months
measure: Conversion rate, defined as the proportion of patients whose baseline cholecalciferol deficiency is corrected (UPCI study)
timeFrame: At 6 months
measure: Change in peripheral muscle strength assessed by squat test (RPCI/UB study)
timeFrame: Baseline to 24 weeks
Other outcomes:
measure: Change in correlative biomarkers of lung cancer risk, inflammation, and pulmonary function (UPCI study)
timeFrame: Baseline to up to 1 year
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Martin Mahoney
role: PRINCIPAL_INVESTIGATOR
References: