Hypoxic Pulmonary Vasoconstriction Pilot Study

Eric A. Hoffman

Status and phase: Completed; Phase 4

Conditions: Emphysema

Treatments: Drug: Sildenafil study group

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03733470

201101707

5R01HL112986 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 30 to 60 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 2 patient groups

Nonsusceptible Smokers (NS)

Experimental group

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.

Treatment:

Drug: Sildenafil study group

Susceptible Smokers (SS)

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil study group