This phase IV trial studies how well a smoking cessation program with or without sildenafil works in decreasing inflammation in the lungs of smokers. Smoking cessation programs may help smokers to quit smoking. Sildenafil is a drug that is approved for many different uses including the treatment of pulmonary hypotension and may have an effect on the blood flow in possible injured areas of the lungs. Even if a smoker stops smoking, the harmful effects caused by previous smoking may recruit inflammatory cells to those affected areas, leading to lung injury. This inflammation combined with irregular blood flow in the lungs may lead to emphysema. This study's goal is to measure and compare individual responses to smoking cessation with or without sildenafil, and imaging of the lungs using non-contrast and contrast CT scans to see if there is a possible decrease of inflammation and an increase of blood flow in the lungs.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03382106.
PRIMARY OBJECTIVES:
I. Heterogeneity of pulmonary blood volume (PBV) assessed during normoxic versus (vs.) hyperoxic breathing will differentiate emphysema susceptible smokers (SS) from non-susceptible smokers (NS) and will test a linkage between PBV heterogeneity observed under normoxia to hypoxia/hyperoxia responsiveness.
II. Heterogeneity of PBV assessed during normoxic vs. hypoxic breathing will differentiate SS from NS and will test a linkage between PBV heterogeneity observed under normoxia to hypoxia/hyperoxia responsiveness.
III. Nitric oxide mediated pulmonary arterial flow plays a primary role in inhibiting hypoxic pulmonary vasoconstriction (HPV) in areas of smoking-associated edema.
IV. Use single photon emission computed tomography (SPECT) imaging of radiolabeled neutrophils to assess regional inflammation in both SS and NS smokers to evaluate whether the amount of inflammation distinguishes these two groups.
V. Smoking cessation alone may not reduce increased density associated with lung injury and thus does not alter the increased PBV heterogeneity in emphysema susceptible smokers.
Va. Smoking cessation combined with tadalafil (Cialis) treatment will enhance resolution of computed tomography (CT) lung density-based indices of smoking induced regional lung injury in emphysema susceptible subjects.
OUTLINE: Participants are randomized to 1 of 4 groups.
SMOKING CESSATION GROUP I: Participants complete smoking cessation program and receive sildenafil orally (PO) three times daily (TID) on days 1-90 in the absence of unacceptable toxicity. Patients also undergo 3 non-contrast CT scans and 2 contrast CT scans at baseline, 2 non-contrast CT scans on days 30 and 60, and 3 non-contrast CT scans and 1 contrast CT scan on day 90.
SMOKING CESSATION GROUP II: Participants complete smoking cessation program and receive placebo PO TID on days 1-90 in the absence of unacceptable toxicity. Patients also undergo 3 non-contrast CT scans and 2 contrast CT scans at baseline, 2 non-contrast CT scans on days 30 and 60, and 3 non-contrast CT scans and 1 contrast CT scan on day 90.
NON-SMOKERS GROUP I: Participants receive sildenafil PO TID on days 1-90 in the absence of unacceptable toxicity. Patients also undergo 3 non-contrast CT scans and 2 contrast CT scans at baseline, 2 non-contrast CT scans on days 30 and 60, and 3 non-contrast CT scans and 1 contrast CT scan on day 90.
NON-SMOKERS GROUP II: Participants undergo 3 non-contrast CT scans and 2 contrast CT scans at baseline, 2 non-contrast CT scans on days 30 and 60, and 3 non-contrast CT scans and 1 contrast CT scan on day 90.
Lead OrganizationUniversity of Iowa/Holden Comprehensive Cancer Center
Principal InvestigatorEric Hoffman
