Emphysema
Conditions
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.
Interventions
DRUGSildenafil study group
One dose of 20 mg Sildenafil will be given one hour before CT imaging.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Eric A. Hoffman
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration | 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. |
Countries
United States
Participant flow
Pre-assignment details
Of 22 subjects, 3 were eliminated because of blood pressure or asthma medications leaving 8NS and 11SS subjects.
Participants by arm
| Arm | Count |
|---|---|
| Nonsusceptible Smokers (NS) 8 emphysema nonsusceptible smokers 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. | 7 |
| Susceptible Smokers (SS) 11 emphysema susceptible smokers 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. | 10 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | PI Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Nonsusceptible Smokers (NS) | Susceptible Smokers (SS) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 10 Participants | 17 Participants |
| Region of Enrollment United States | 7 participants | 10 participants | 17 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 11 |
| other Total, other adverse events | 0 / 8 | 0 / 11 |
| serious Total, serious adverse events | 0 / 8 | 0 / 11 |
Outcome results
Primary
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.
Time frame: Change of perfused blood volume from baseline at one hour after sildenafil administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nonsusceptible Smokers (NS) | Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration | 0.37 coefficient of variation | Standard Deviation 0.03 |
| Susceptible Smoker (SS) | Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration | 0.42 coefficient of variation | Standard Deviation 0.09 |
p-value: <0.05t-test, 2 sided