Hypoxic Pulmonary Vasoconstriction Pilot Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Emphysema

Intervention / Treatment
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* Drug: Sildenafil study group


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nonsusceptible Smokers (NS)<br>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<br>* One dose of 20 mg Sildenafil will be given one hour before CT imaging.<br>* Other names: Revatio;|
| Experimental: Susceptible Smokers (SS)<br>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<br>* One dose of 20 mg Sildenafil will be given one hour before CT imaging.<br>* Other names: Revatio;|

What is the study measuring?
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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. |