Smoking Cessation and Functional CT Assessment

Eric A. Hoffman

Status and phase: Completed; Phase 4

Conditions: Emphysema

Treatments: Drug: Sildenafil 20 MG; Diagnostic Test: Pressure wave reflection; Diagnostic Test: Pulse wave velocity; Drug: Placebo Oral Tablet; Diagnostic Test: Carotid artery compliance and stiffness

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03382106

201706713

R01HL130883 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The investigators will study the effect of pulmonary arterial vasodilation to see if it eliminates indices of persistent lung injury in smokers that are susceptible to emphysema.

Full description

The purpose of this research study is to find out if smoking cessation combined with sildenafil, an FDA approved drug for pulmonary hypertension, will decrease inflammation in the lung. 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. In about 30-40% of smokers, this inflammation combined with irregular blood flow in the lungs may lead to emphysema. The study goal is to measure and compare individual responses to smoking cessation, Sildenafil and placebo used three times per day, 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. The study also intends to see if using Sildenafil three times per day, in addition to smoking cessation will restore blood flow to the possible injured areas of the lungs. Sildenafil is an FDA approved medication for pulmonary hypertension but will be used off-label to study the effects it may or may not have on the blood flow in possible injured areas of the lungs. Non-smokers will be enrolled to compare lung imaging and the effects of Sildenafil on their lungs with that of smokers undergoing a smoking cessation program with placebo or Sildenafil. Non-smokers will complete identical measurements as smokers, with Sildenafil used three times per day or no medication across a similar 90 day period of time. Vascular measurements of pulse wave velocity, carotid artery compliance/stiffness and pressure wave reflection will be done at baseline and 90 day visits.

Enrollment: 162 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (Smokers):

• Between the age of 21 to 65 at baseline
• Be willing to participate in a smoking cessation program
• Be willing to attend all clinic visits
• Must be currently smoking at least ½ pack/day at baseline (confirmed with cotinine level and CO Smokerlyzer)
• >5 pack-year history of smoking
• Global Initiative for Chronic Obstructive Lung Disease (GOLD) 0: FEV1≥0.80 and FEV1/FVC>0.70 Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC)
• GOLD 1: FEV1≥0.80 and FEV1/FVC < 0.70
• GOLD 2: 0.50≤FEV1<0.80 and FEV1/FVC < 0.70
• Be willing to abstain from using any nicotine patches, e-cigarettes, or marijuana for the duration of the study.

Inclusion Criteria (Non-smokers):

• Between the age of 21 to 65 at baseline
• Be willing to attend all clinic visits
• Have never smoked (confirmed with cotinine level and CO smokerlyzer)
• GOLD 0: FEV1≥0.80 and FEV1/FVC>0.70

Exclusion Criteria (Smokers and Non-smokers):

• Women only: Cannot be pregnant or nursing at baseline or plan to become pregnant during the course of the study
• Body Mass Index (BMI) > 35
• Allergies to shell fish, seafood, eggs or iodine
• Heart disease, kidney disease or diabetes
• Diagnosis of asthma
• Any metal in or on the body (that cannot be removed) between the nose and the abdomen
• Any major organ system disease (by judgment of the study medical team)
• A glomerular filtration rate of 60 cc per minute or less.
• Nitroglycerin usage or nitrates and use of phosphodiesterase 5 (PDE5) inhibitors
• Prior history of hypersensitivity to sildenafil
• Currently prescribed a phosphodiesterase (PDE) inhibitors medication (ex: Viagra, Cialis, etc)
• Known Pulmonary Hypertension
• Has used e-cigarettes and marijuana <1 years
• Use of ACE Inhibitors, Calcium Channel Blockers, Angiotensin II Receptor Blockers for control of blood pressure or any combination of these three types of medications.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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162 participants in 4 patient groups, including a placebo group

Smoking Cessation Group 1

Experimental group

Description:

80 normal smokers will be recruited (defined by Pulmonary Function Tests, questionnaires and interviews), between the ages of 21 and 65 will be studied to assess inflammation and heterogeneity of Perfused Blood Volume prior to and following a 3 month smoking cessation program. In 40 of the 80 subjects during the smoking cessation program, we will provide three times per day Sildenafil 20 milligrams (MG) (Viagra) for the full 3 months of the smoking cessation period. We select a three-month cessation program to maximize the likelihood of compliance with cessation yet providing enough time for a resolution of lung injury to take place. Pulse wave velocity, carotid artery compliance and stiffness and pressure wave reflection will be measured.

Treatment:

Diagnostic Test: Carotid artery compliance and stiffness

Diagnostic Test: Pulse wave velocity

Diagnostic Test: Pressure wave reflection

Drug: Sildenafil 20 MG

Smoking Cessation Group 2

Placebo Comparator group

Description:

80 normal smokers will be recruited (defined by Pulmonary Function Tests, questionnaires and interviews), between the ages of 21 and 65 will be studied to assess inflammation and heterogeneity of Perfused Blood Volume prior to and following a 3 month smoking cessation program. In 40 of the 80 subjects during the smoking cessation program, we will provide three times per day placebo oral tablet for the full 3 months of the smoking cessation period. We select a three-month cessation program to maximize the likelihood of compliance with cessation yet providing enough time for a resolution of lung injury to take place. Pulse wave velocity, carotid artery compliance and stiffness and pressure wave reflection will be measured.

Treatment:

Diagnostic Test: Carotid artery compliance and stiffness

Drug: Placebo Oral Tablet

Diagnostic Test: Pulse wave velocity

Diagnostic Test: Pressure wave reflection

Non-Smokers Group 1

Experimental group

Description:

20 non-smokers will be recruited (defined by Pulmonary Function Tests, questionnaires and interviews) between the ages of 21 and 65 will be studied to compare the heterogeneity of Perfused Blood Volume with that of smokers for a 3 month period of time. We will provide 10 females and 10 males three times per day Sildenafil 20 milligrams (MG) (Viagra) for the full 3 months.

Treatment:

Diagnostic Test: Carotid artery compliance and stiffness

Diagnostic Test: Pulse wave velocity

Drug: Sildenafil 20 MG

Non-Smokers Group 2

No Intervention group

Description:

20 non-smokers will be recruited (defined by Pulmonary Function Tests, questionnaires and interviews) between the ages of 21 and 65 will be studied to compare the heterogeneity of Perfused Blood Volume with that of smokers for a 3 month period of time. 10 females and 10 males will not receive any medication for the full 3 months.