Back to resultsSmoking Cessation and Functional CT Assessment
Primary Purpose
Emphysema
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sildenafil 20 MG
Placebo Oral Tablet
Pulse wave velocity
Carotid artery compliance and stiffness
Pressure wave reflection
Sponsored by
About this trial
This is an interventional basic science trial for Emphysema
Eligibility 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.
Sites / Locations
- University of Iowa Hospitals and ClinicsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
No Intervention
Arm Label
Smoking Cessation Group 1
Smoking Cessation Group 2
Non-Smokers Group 1
Non-Smokers Group 2
Arm 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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Carotid beta-stiffness index
Our outcome measure is the difference of common carotid artery stiffness between baseline and 90 day visits
Carotid augmentation index
Our outcome measure is the difference of pressure wave reflection between baseline and 90 day visits
Full Information
NCT ID
NCT03382106
First Posted
December 5, 2017
Last Updated
July 12, 2023
Sponsor
Eric A. Hoffman
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT03382106
Brief Title
Smoking Cessation and Functional CT Assessment
Official Title
Smoking Cessation and Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 19, 2018 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eric A. Hoffman
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Emphysema
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Subject and study team are masked to which arm subject is assigned (study drug or placebo). Investigational pharmacy will not be masked. For the non-smoker groups, both subjects and the study team will know which group they are assigned to (study drug or no medication).
Allocation
Randomized
Enrollment
280 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Smoking Cessation Group 1
Arm Type
Experimental
Arm 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.
Arm Title
Smoking Cessation Group 2
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Non-Smokers Group 1
Arm Type
Experimental
Arm 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.
Arm Title
Non-Smokers Group 2
Arm Type
No Intervention
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Sildenafil 20 MG
Other Intervention Name(s)
Experimental: Smoking Cessation Group 1, Experimental: Non-Smokers Group 1
Intervention Description
Sildenafil, 20mg three times daily for 3 month period.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
No Intervention: Smoking Cessation Group 2
Intervention Description
Placebo manufactured to look like Sildenafil 20 MG
Intervention Type
Diagnostic Test
Intervention Name(s)
Pulse wave velocity
Intervention Description
Vascular pulse measurement at the radial, brachial, femoral, and carotid arteries are taken using a tonometer probe.
Intervention Type
Diagnostic Test
Intervention Name(s)
Carotid artery compliance and stiffness
Intervention Description
An echocardiogram is done by using a probe placed on the skin.
Intervention Type
Diagnostic Test
Intervention Name(s)
Pressure wave reflection
Intervention Description
Carotid pulse measurement taken using a tonometer probe
Primary Outcome Measure Information:
Title
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.
Description
Our outcome measure is the change in regional blood volume between baseline and interventions with CT imaging, sildenafil/placebo and smoking cessation.
Time Frame
90 Days
Secondary Outcome Measure Information:
Title
Pulse wave velocity of carotid radial, brachial, femoral and carotid arteries
Description
Our outcome measure is the difference of arterial stiffness between baseline and 90 day visits.
Time Frame
Baseline and 90 day
Title
Carotid beta-stiffness index
Description
Our outcome measure is the difference of common carotid artery stiffness between baseline and 90 day visits
Time Frame
Baseline and 90 Day
Title
Carotid augmentation index
Description
Our outcome measure is the difference of pressure wave reflection between baseline and 90 day visits
Time Frame
Baseline and 90 Day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sue E Salisbury, BS
Phone
319-356-1810
Email
sue-salisbury@uiowa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Maren Rogers
Phone
319-353-6213
Email
maren-rogers@uiowa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Hoffman, PhD
Organizational Affiliation
Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Smoking Cessation and Functional CT Assessment
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