Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema

NCT02682147 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 201508782R01HL130883
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study will use dual energy x-ray computed tomography (DECT) to evaluate the relationship between heterogeneous perfusion, hypoxia (low oxygen in inspired gas) and induction of pulmonary vascular dilatation to characterize emphysema susceptibility in a normal smoking population. The investigators will correlate DECT measures of perfusion with lung injury measured by single photon emission computed tomography (SPECT). 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 (2)

• Perfused blood volume assessed pre and post sildenafil administration in susceptible smoker (SS) subjects.

  Regional heterogeneity perfused blood volume will be measured by duel energy CT scan at two time points and compared at two points, pre and post the administration of sildenafil.

  Pre sildenafil adminstration and one hour after sildenafil adminstration.

• Perfused blood volume assessed pre and post sildenafil administration in non-susceptible smoker (SS) subjects.

  Regional heterogeneity perfused blood volume will be measured by duel energy CT scan at two time points and compared at two points, pre and post the administration of sildenafil.

  Pre sildenafil adminstration and one hour after sildenafil adminstration.

Study Arms (1)

Sildenafil

EXPERIMENTAL

40 subjects (20M and 20F) will be recruited to study non-contrast imaging at TLC and 20%VC and with contrast using DECT scans to assess perfused blood volume. For the intervention, the subject will be administered 20 mg of sildenafil and then the same scanning will be repeated one hour after sildenafil administration.

Drug: Sildenafil

Interventions

Sildenafil DRUG

One dose of 20 mg Sildenafil will be given one hour before CT imaging.

Also known as: Revatio

Sildenafil

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be between the ages of 25 and 65.
• Must be currently smoking at least 1/2 pack/day (confirmed with cotinine level).
• Must have pulmonary function test (PFT) results that meet the following (there will be two groups):
• Group 1:
• Forced expiratory volume at one second (FEV1)/Forced vital capacity (FVC) \> 70%
• Forced Expiratory Flow at 25-75% of predicted(FEF25-75) \> 79% of predicted
• FVC greater than 80% of predicted
• Group 2:
• For subjects with mild lung impairment:
• FEV1\>80% of predicted
• FEV1/FVC\<0.7
• Must be able to give informed consent for self.

You may not qualify if:

• Pregnant or breastfeeding females.
• Body Mass Index (BMI) greater than 32.
• Weight of greater than 220 pounds (100 kg).
• Allergies to shell fish, seafood, eggs or iodine.
• Heart disease, kidney disease or diabetes.
• Diagnosis of asthma.
• Usage of any medications that are known to affect the heart or lungs (contraceptives, anti-depressants, analgesics EXCEPT aspirin, antihypertensives, and medications for osteoporosis and gastrointestinal diseases will be allowed).
• Any metal in or on the body between the nose and the abdomen.
• Any major organ system disease (by judgment of study medical team).
• A glomerular filtration rate of 60 cc per minute or less.
• Nitroglycerin usage or nitrates (in addition to nitroglycerin) and use of phosphodiesterase 5 (PDE5) inhibitors within the previous 7 days of the study date.
• Prior history of hypersensitivity to Sildenafil.

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

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• Alford SK, van Beek EJ, McLennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7485-90. doi: 10.1073/pnas.0913880107. Epub 2010 Apr 5.

  PMID: 20368443 RESULT

• Iyer KS, Newell JD Jr, Jin D, Fuld MK, Saha PK, Hansdottir S, Hoffman EA. Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease. Am J Respir Crit Care Med. 2016 Mar 15;193(6):652-61. doi: 10.1164/rccm.201506-1196OC.

  PMID: 26569033 RESULT

MeSH Terms

Conditions

Emphysema

Interventions

Sildenafil Citrate

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

Study Officials

• Eric A Hoffman, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: February 15, 2016
• Study Start: July 10, 2017
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: April 15, 2025

Record last verified: 2025-04

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. This costs will not exceed $250. This service will be available for a minimum of 2 years of study close.

Locations

US (1)