Smoking Cessation and Functional CT Assessment

Smoking Cessation and Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema

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.

Study Overview

• Status: Completed
• Conditions: Emphysema
• Intervention / Treatment: Drug: Sildenafil 20 MG; Diagnostic test: Pulse wave velocity; Diagnostic test: Carotid artery compliance and stiffness; Diagnostic test: Pressure wave reflection; Drug: Placebo Oral Tablet

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Smoking Cessation Group 1; 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.	Drug: Sildenafil 20 MG; Sildenafil, 20mg three times daily for 3 month period.; Other Names: Experimental: Smoking Cessation Group 1; Experimental: Non-Smokers Group 1; Diagnostic test: Pulse wave velocity; Vascular pulse measurement at the radial, brachial, femoral, and carotid arteries are taken using a tonometer probe.; Diagnostic test: Carotid artery compliance and stiffness; An echocardiogram is done by using a probe placed on the skin.; Diagnostic test: Pressure wave reflection; Carotid pulse measurement taken using a tonometer probe
Placebo Comparator: Smoking Cessation Group 2; 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.	Diagnostic test: Pulse wave velocity; Vascular pulse measurement at the radial, brachial, femoral, and carotid arteries are taken using a tonometer probe.; Diagnostic test: Carotid artery compliance and stiffness; An echocardiogram is done by using a probe placed on the skin.; Diagnostic test: Pressure wave reflection; Carotid pulse measurement taken using a tonometer probe; Drug: Placebo Oral Tablet; Placebo manufactured to look like Sildenafil 20 MG; Other Names: No Intervention: Smoking Cessation Group 2
Experimental: Non-Smokers Group 1; 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.	Drug: Sildenafil 20 MG; Sildenafil, 20mg three times daily for 3 month period.; Other Names: Experimental: Smoking Cessation Group 1; Experimental: Non-Smokers Group 1; Diagnostic test: Pulse wave velocity; Vascular pulse measurement at the radial, brachial, femoral, and carotid arteries are taken using a tonometer probe.; Diagnostic test: Carotid artery compliance and stiffness; An echocardiogram is done by using a probe placed on the skin.
No Intervention: Non-Smokers Group 2; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure and compare individual smokers' responses to smoking cessation, Sildenafil and placebo with lung imaging to determine decrease of inflammation and increase of blood flow in lungs.	Our outcome measure is the change in regional blood volume between baseline and interventions with CT imaging, sildenafil/placebo and smoking cessation.	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse wave velocity of carotid radial, brachial, femoral and carotid arteries	Our outcome measure is the difference of arterial stiffness between baseline and 90 day visits.	Baseline and 90 day
Carotid beta-stiffness index	Our outcome measure is the difference of common carotid artery stiffness between baseline and 90 day visits	Baseline and 90 Day
Carotid augmentation index	Our outcome measure is the difference of pressure wave reflection between baseline and 90 day visits	Baseline and 90 Day

Collaborators and Investigators

• Sponsor: Eric A. Hoffman
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Eric Hoffman, PhD, Professor

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): September 24, 2024
• Study Completion (Actual): September 24, 2024

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Vasodilator Agents; Urological Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 201706713; R01HL130883 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CT images will be shared including non-contrast images at TLC, FRC and RV as well as dual energy CT image data used to assess regional perfused blood volume. All associated pulmonary function test results will be shared. CT-derived metrics.
• IPD Sharing Time Frame: Data will be made available starting 6 months after publication of the primary results of each aim.
• IPD Sharing Access Criteria: Data will be provided to academic-based researchers upon written request to the PI, Eric A. Hoffman, PhD. A nominal charge will be made for the time it takes for a technician to prepare and transfer the requested data. These costs will not exceed $250. This service will be available for a minimum of 2 years of study close.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No