Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Bone Density Conservation Agents

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Vitamins

Vitamin D

Cholecalciferol

Vitamin A

Retinol palmitate

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Retinol

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.

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.

multivitamin

Placebo

David Wilson, MD

This study aims to establish the ability of 4,000 IU oral vitamin D3 per day (in combination with a daily multivitamin) to safely convert vitamin D3-deficient subjects at increased risk of lung cancer to a vitamin D3-sufficient state, and to explore effects of vitamin D3 supplementation in this population on markers of inflammation and lung cancer risk. Current and former smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and represent the clinical population of interest for this study.

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.

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)

The proportion of subjects whose baseline vitamin D3 deficiency is corrected after 12 months of supplementation (i.e., the 12-month conversion rate).

Effect of vitamin D supplementation on lung function as measured by spirometry will be evaluated.

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.

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.

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.

National Cancer Institute (NCI)

University of Pittsburgh

MD, MPH, Associate Professor of Medicine

Multiple Pulmonary Nodules

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Other Dietary Supplements

Curcumin

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Enzyme Inhibitors

Omega 3 Fatty Acid

Group A:

4 grams Lovaza®, 2 grams twice a day (BID). 2 grams by mouth daily, AM and PM 8,000 mgs CUR Curcumin C3 complex® tablets, divided into 2 doses. 4 grams by mouth, twice a day, AM and PM.

Group B:

2 grams Lovaza®, 1 gram twice a day, AM and PM. 4,000 mgs CUR Curcumin C3 complex® tablets, 2,000 mgs twice a day, AM and PM.

1 placebo capsule twice a day, AM and PM.

Placebo: Two matching placebo capsules twice a day (BID), taken by mouth, AM and PM

Groups A and B as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.

Curcumin C3 complex®

Lovaza®

Groups B and Placebo as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.

Arnay Marshall

Nagi Kumar, Ph.D.

Nagi Kumar, PhD

Mark Alexandrow, PhD

Jhanelle Gray, MD

Tawee Tanventyanon, MD

Michael Alberts, MD

Lary Robinson, MD

Farah Khalil, MD

Donald Klippenstein, MD

Matthew Schabath, PhD

Michael Schell, PhD

Nagi Kumar, Ph.D

The purpose of this study is to find out if an investigational combination drug called Lovaza (made with fish oils)+Curcumin C3 Complex (made from a root called curcumin) can help reduce the size of lung nodules. Researchers also want to find out if the combination of Lovaza+Curcumin C3 Complex is safe and tolerable.

Phase II Trial to Modulate Intermediate Endpoint Biomarkers in Former and Current Smokers

Phase II Trial of Investigational Agents to Modulate Intermediate Endpoint Biomarkers, Including Pulmonary Nodules, in Former and Current Smokers

Difference in the average change in bronchial nodule size from baseline to end of therapy at 6 months for each study arm. A lower size is taken to be the desired value for participants receiving study drug, assuming an increase in size for the placebo arm.

Number of nodules ≥4 mm per study arm, post treatment.

Rate of participant adherence per study arm. Proof of adherence based on study team pill counts, participant diet logs and pill logs at end of study, vs. data collected at midpoint.

Safety of the combined agents (Curcumin C3 complex® + Lovaza®) at 2 dose arms vs. placebo as indicated by incidence of related adverse events and toxicities, monitored using Common Toxicity Criteria version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Pittsburgh Vitamin D Study: Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer	NCT02532062	Deficiency of V... COPD	Cholecalciferol multivitamin Placebo	50 Years - 85 Years	University of Pittsburgh
The Pittsburgh Vitamin D Study: Vitamin D Supplementation in Vitamin D-deficient Subjects at Risk of Lung Cancer	NCT02532062	Deficiency of V... COPD	Cholecalciferol multivitamin Placebo	50 Years - 85 Years	University of Pittsburgh
Phase II Trial to Modulate Intermediate Endpoint Biomarkers in Former and Current Smokers	NCT03598309	Lung Diseases Lung Cancer, Pr...	Curcumin C3 com... Lovaza® Placebo	55 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for lung cancer risk