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Hypoxic Pulmonary Vasoconstriction Pilot Study

Primary Purpose

Emphysema

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Sildenafil study group

About this trial

This is an interventional basic science trial for Emphysema

Eligibility Criteria

30 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

University of Iowa

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Nonsusceptible Smokers (NS)

Susceptible Smokers (SS)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03733470

First Posted

October 23, 2018

Last Updated

September 12, 2019

Sponsor

Eric A. Hoffman

Collaborators

National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT03733470

Brief Title

Hypoxic Pulmonary Vasoconstriction Pilot Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

June 29, 2011 (Actual)

Primary Completion Date

January 13, 2014 (Actual)

Study Completion Date

January 13, 2014 (Actual)

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

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

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

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nonsusceptible Smokers (NS)

Arm Type

Experimental

Arm Description

Arm Title

Susceptible Smokers (SS)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sildenafil study group

Other Intervention Name(s)

Revatio

Intervention Description

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

Primary Outcome Measure Information:

Title

Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration

Description

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.

Time Frame

Change of perfused blood volume from baseline at one hour after sildenafil administration.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric A Hoffman

Organizational Affiliation

University of Iowa

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

20368443

Citation

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.

Results Reference

result

Available IPD and Supporting Information:

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

http://www.i-clic.uihc.uiowa.edu/

Available IPD/Information Identifier

Data Distribution

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Hypoxic Pulmonary Vasoconstriction Pilot Study

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