- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02532062
The Pittsburgh Vitamin D Study: Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer
Efficacy of Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer (The Pittsburgh Vitamin D Study)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Smoking avoidance or cessation are essential to the prevention of lung cancer. However, not all smokers are able to quit smoking and, importantly, former smokers remain at increased risk of lung cancer compared to never smokers. Despite smoking prevention/cessation programs and treatment advances, lung cancer is still the leading cause of cancer-related mortality in the United States with more than 158,000 individuals expected to die from this disease in 2015. Effective and safe prevention strategies are expected to be more successful in reducing lung cancer deaths than treatment of established disease.
NF-kappaB (NF-kB) pathway activation underlies smoking-related inflammation and lung carcinogenesis, and those agents which suppress NF-κB signaling may have the potential to prevent lung cancer. Recent preclinical data from our group and others indicate that the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has lung cancer chemopreventive activity. Because systemic 1,25(OH)2D3 administration is complicated by its hypercalcemia-inducing properties, the investigators propose to use oral supplementation with vitamin D3 (cholecalciferol) to safely achieve chemopreventive 1,25(OH)2D3 levels within the lung.
This randomized, placebo-controlled Phase IIb study aims to evaluate the ability of 4,000 IU oral vitamin D3/day (in combination with a daily multivitamin) to safely convert vitamin D3-deficient subjects at risk of lung cancer to a vitamin D3-sufficient state.
Study participants will be recruited from among Pittsburgh Lung Screening Study Extension (PLuSS-X) and PLuSS-XX participants not diagnosed with lung cancer, and from among the patient population seen by the PI of this protocol. The study consists of two stages, a screening and an intervention stage, with their own consent forms. In Stage 1 (the screening stage), the vitamin D3 status of subjects potentially eligible for participation in the intervention will be determined; in Stage 2 (the intervention stage), supplementation with oral vitamin D3 will be evaluated.
Participants who fulfill the eligibility criteria and provided signed consent for Stage 2 will be randomized in a 2:1 ratio to receive: (A) 4,000 IU vitamin D3 plus a multivitamin (containing 400 IU vitamin D3) daily for one year, or (B) a placebo vitamin D3 pill plus a multivitamin daily for one year. Both groups will contain equal numbers of current and ex-smokers; in total 120 subjects will be randomized. To evaluate whether supplementation safely corrects vitamin D3 deficiency in this population, blood samples will be obtained at baseline, 3, 6, and 12 months of intervention for evaluation of 25(OH)D3 and serum calcium. The collected blood will also be used to facilitate biomarker assessment. Pulmonary function tests (PFTs) will be obtained at baseline and repeated after 12 months to determine whether supplementation has an effect on lung function. Sputum and nasal epithelium will be collected at baseline, 6 months and 12 months to facilitate biomarker assessment.
- Study Objectives Primary Objective: To establish the 12-month conversion rate (i.e., proportion of subjects whose baseline vitamin D3 deficiency is corrected after 12 months of supplementation).
Secondary Objectives: To determine the 3-month and 6-month conversion rates and examine the effect of vitamin D3 supplementation in current and former smokers. Additionally, to examine the effects of vitamin D3 supplementation on biomarkers of lung cancer risk, inflammation, and pulmonary function.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 50 years old.
- Current or ex-smoker with at least 10 pack-year history
- COPD, GOLD II or greater (defined as FEV1/FVC <70% and FEV1 % predicted <80%)
- 25(OH)D3 level ≤25 ng/mL
- Willingness to comply with study guidelines.
- Willingness to avoid alternative/additional vitamin D3 supplementation for the duration of the trial
- Participant 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 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 participation in another cancer chemoprevention study
- 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.
- Being pregnant
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Supplementation
Participants who are assigned to the Supplementation arm will receive a vitamin D supplement containing 4,000 units of vitamin D3 (cholecalciferol; capsule form) plus an oral multivitamin containing 400 units of vitamin D3 daily for a period of one year.
|
4,000 IU, oral, once a day for one year
Other Names:
oral, once a day for one year
|
Active Comparator: Placebo
Participants who are assigned to the Placebo arm will receive a placebo supplement plus an oral multivitamin containing 400 units of vitamin D3 daily for a period of one year.
|
oral, once a day for one year
oral, once a day for one year
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The 12-month conversion rate
Time Frame: 12 months
|
The proportion of subjects whose baseline vitamin D3 deficiency is corrected after 12 months of supplementation (i.e., the 12-month conversion rate).
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The 3-month conversion rate
Time Frame: 3 months
|
3 months
|
|
The 6-month conversion rate
Time Frame: 6 months
|
6 months
|
|
Pulmonary function as measured by spirometry
Time Frame: 12 months
|
Effect of vitamin D supplementation on lung function as measured by spirometry will be evaluated.
|
12 months
|
Promoter methylation status in sputum and nasal swab samples
Time Frame: 12 months
|
Effect of supplementation on promoter methylation status of genes previously reported associated with lung cancer risk (e.g., RAMP2, p16, MGMT) in sputum and nasal swab samples will be explored.
|
12 months
|
Protein expression in sputum and nasal swab samples
Time Frame: 12 months
|
Effect of supplementation on the expression of proteins, including inflammation and vitamin D metabolism-related proteins, in sputum and nasal swab samples will be explored.
|
12 months
|
Concentration of inflammatory markers in blood
Time Frame: 12 months
|
Blood samples will be analyzed for inflammatory markers such as IL6 and CRP and the effect of supplementation on the examined cytokines will be explored.
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David Wilson, MD, University of Pittsburgh
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO15020031
- P50CA090440 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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