Clinical trial NCT03733470: Hypoxic Pulmonary Vasoconstriction Pilot Study
Official title: Pilot Study for Perfusion Heterogeneity: a Mechanistic Image-Based Emphysema Phenotype
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Emphysema
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-11-07
Enrollment: 22
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration
timeFrame: Change of perfused blood volume from baseline at one hour after sildenafil administration.
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Eric A Hoffman
role: PRINCIPAL_INVESTIGATOR
References:
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.