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Hypoxic Pulmonary Vasoconstriction Pilot Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03733470
Recruitment Status : Completed
First Posted : November 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Eric A. Hoffman, University of Iowa

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.

Condition or disease Intervention/treatment Phase
Emphysema Drug: Hypoxia Administration study group Drug: Hyperoxia Administration study group Drug: Sildenafil study group Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pilot Study for Perfusion Heterogeneity: a Mechanistic Image-Based Emphysema Phenotype
Actual Study Start Date : June 29, 2011
Actual Primary Completion Date : January 13, 2014
Actual Study Completion Date : January 13, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Emphysema

Arm Intervention/treatment
Experimental: Hypoxia administration study group
15 subjects recruited to study normoxia oxygen compared to hypoxia oxygen. Subjects will be evaluated under normoxia oxygen with low dose non-contrast CT at total lung capacity (TLC) and 20% vital capacity (VC) and then with contrast using dual energy (DECT) scans to evaluate heterogeneity of perfused blood volume (PBV). For the intervention, following the normoxia oxygen scans, hypoxia administration will be administered by breathing an inspired oxygen fraction (FIO2) of 15% oxygen and the non-contrast and contrast using DECT scans to evaluate heterogeneity of perfused blood volume will be completed.
Drug: Hypoxia Administration study group
scan completed after 5 minutes of breathing in hypoxic air
Other Name: Oxygen

Experimental: Hyperoxia administration study group
15 subjects recruited to study normoxia oxygen scans compared to hyperoxia oxygen scans. Subjects will be evaluated in each group under normoxia oxygen with low dose non-contrast CT scans at TLC and 20% vital capacity (VC) and then with contrast scans using DECT to evaluate heterogeneity of perfused blood volume (PBV). For the intervention, following the normoxia scans, hyperoxia administration will be administered by breathing an inspired FIO2 of 100% oxygen and the non-contrast and contrast using DECT to evaluate heterogeneity of perfused blood volume will be completed.
Drug: Hyperoxia Administration study group
scan completed after 5 minutes of breathing in hyperoxic air
Other Name: Oxygen

Experimental: Sildenafil study group
15 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 Name: Revatio




Primary Outcome Measures :
  1. Perfused blood volume assessed for a change in lung inflammation pre and post dose sildenafil administration [ Time Frame: Change of perfused blood volume from baseline at one hour after 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.

  2. Perfused blood volume assessed for a change in lung inflammation pre and post hypoxic breathing [ Time Frame: Change of perfused blood volume from baseline at one hour after post hypoxic administration. ]
    Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post hypoxic breathing.



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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03733470


Locations
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United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Eric A. Hoffman
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Eric A Hoffman University of Iowa

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: Data Distribution

Publications of Results:
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Responsible Party: Eric A. Hoffman, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT03733470     History of Changes
Other Study ID Numbers: 201101707
5R01HL112986 ( U.S. NIH Grant/Contract )
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Informed Consent Form (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, 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.

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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

Additional relevant MeSH terms:
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Emphysema
Pulmonary Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents