Smoking Cessation and Functional CT Assessment

NCT03382106 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: 201706713R01HL130883
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

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.

Conditions

Emphysema

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Pulse wave velocity of carotid radial, brachial, femoral and carotid arteries

  Baseline and 90 day

• Carotid beta-stiffness index

  Baseline and 90 Day

• Carotid augmentation index

  Baseline and 90 Day

Study Arms (4)

Smoking Cessation Group 1

EXPERIMENTAL

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; Diagnostic Test: Pulse wave velocity; Diagnostic Test: Carotid artery compliance and stiffness; Diagnostic Test: Pressure wave reflection

Smoking Cessation Group 2

PLACEBO COMPARATOR

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.

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

Non-Smokers Group 1

EXPERIMENTAL

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; Diagnostic Test: Pulse wave velocity; Diagnostic Test: Carotid artery compliance and stiffness

Non-Smokers Group 2

NO INTERVENTION

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.

Interventions

Sildenafil 20 MG DRUG

Sildenafil, 20mg three times daily for 3 month period.

Also known as: Experimental: Smoking Cessation Group 1, Experimental: Non-Smokers Group 1

Non-Smokers Group 1; Smoking Cessation Group 1

Placebo Oral Tablet DRUG

Placebo manufactured to look like Sildenafil 20 MG

Also known as: No Intervention: Smoking Cessation Group 2

Smoking Cessation Group 2

Pulse wave velocity DIAGNOSTIC_TEST

Vascular pulse measurement at the radial, brachial, femoral, and carotid arteries are taken using a tonometer probe.

Non-Smokers Group 1; Smoking Cessation Group 1; Smoking Cessation Group 2

Carotid artery compliance and stiffness DIAGNOSTIC_TEST

An echocardiogram is done by using a probe placed on the skin.

Non-Smokers Group 1; Smoking Cessation Group 1; Smoking Cessation Group 2

Pressure wave reflection DIAGNOSTIC_TEST

Carotid pulse measurement taken using a tonometer probe

Smoking Cessation Group 1; Smoking Cessation Group 2

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eric A. Hoffman: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Emphysema

Interventions

Sildenafil Citrate; Pulse Wave Analysis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Eric Hoffman, PhD

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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).
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 22, 2017
• Study Start: March 19, 2018
• Primary Completion: September 24, 2024
• Study Completion: September 24, 2024
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available starting 6 months after publication of the primary results of each aim.
• 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.

Locations

US (1)