Hypoxic Pulmonary Vasoconstriction Pilot Study

Pilot Study for Perfusion Heterogeneity: a Mechanistic Image-Based Emphysema Phenotype

The purpose of this study is to determine if the events leading to smoking-associated centrilobular and paraseptal emphysema are caused by a failure of the lungs' inherent mechanisms to block hypoxic pulmonary vasoconstriction (HPV) in areas of smoking-induced inflammation.

Study Overview

• Status: Completed
• Conditions: Emphysema
• Intervention / Treatment: Drug: Sildenafil study group

Detailed Description

Overall goals of this study are to 1) determine the effects on sildenafil on the heterogeneity perfused blood volume in smokers susceptible to emphysema using dual energy CT 2) utilize pulmonary blood volume heterogeneity as an image-based biomarker to differentiate normal and susceptible smokers.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be between the ages of 30 and 60.
• 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:
• Forced Expiratory Volume at one second (FEV1)/Forced Vital Capacity (FVC) > 70%
• Forced Expiratory Flow at 25-75% (FEF25-75) > 79% of predicted
• FVC greater than 80% of predicted
• Must be able to give informed consent for self.

Exclusion Criteria:

• 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).

For the subjects that will receive Sildenafil as part of the study, additional exclusion criteria are as follows:

• Nitroglycerin usage.
• Prior history of hypersensitivity to Sildenafil.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nonsusceptible Smokers (NS); 8 subjects recruited to study non-contrast imaging at TLC and 20%VC and with contrast using DECT 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 study group; One dose of 20 mg Sildenafil will be given one hour before CT imaging.; Other Names: Revatio
Experimental: Susceptible Smokers (SS); 11 subjects recruited to study non-contrast imaging at TLC and 20% VC and with contrast using DECT to assess pefused 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 study group; One dose of 20 mg Sildenafil will be given one hour before CT imaging.; Other Names: Revatio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration	Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post the administration of sildenafil.	Change of perfused blood volume from baseline at one hour after sildenafil administration.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2011
• Primary Completion (Actual): January 13, 2014
• Study Completion (Actual): January 13, 2014

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 201101707; 5R01HL112986 (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 Total Lung Capacity (TLC), Functional Residual Capacity (FRC) and Residual Volume (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, Ph.D. 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: Data Distribution

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