The Pittsburgh Vitamin D Study: Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02532062|
Recruitment Status : Recruiting
First Posted : August 25, 2015
Last Update Posted : June 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Deficiency of Vitamin D3 COPD||Dietary Supplement: Cholecalciferol Dietary Supplement: multivitamin Dietary Supplement: Placebo||Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Efficacy of Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer (The Pittsburgh Vitamin D Study)|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||September 2019|
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.
Dietary Supplement: Cholecalciferol
4,000 IU, oral, once a day for one year
Other Name: Vitamin D3Dietary Supplement: multivitamin
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.
Dietary Supplement: multivitamin
oral, once a day for one yearDietary Supplement: Placebo
oral, once a day for one year
- 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).
- The 3-month conversion rate [ Time Frame: 3 months ]
- The 6-month conversion rate [ Time Frame: 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.
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02532062
|Contact: David Wilson, MDemail@example.com|
|Contact: Brenda Diergaarde, PhDfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: David Wilson, MD 412-687-3355 email@example.com|
|Contact: Brenda Diergaarde, PhD 412-623-5891 firstname.lastname@example.org|
|Principal Investigator:||David Wilson, MD||University of Pittsburgh|