Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-10

Study Completion Date

2025-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study will use dual energy x-ray computed tomography (DECT) to evaluate the relationship between heterogeneous perfusion, hypoxia (low oxygen in inspired gas) and induction of pulmonary vascular dilatation to characterize emphysema susceptibility in a normal smoking population. The investigators will correlate DECT measures of perfusion with lung injury measured by single photon emission computed tomography (SPECT). The investigators will study the effect of pulmonary arterial vasodilation to see if it eliminates indices of persistent lung injury in smokers that are susceptible to emphysema

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Inhalation Profiling of Idiopathic Pulmonary Fibrosis (IPF) Patients

NCT02058602

Idiopathic Pulmonary Fibrosis

COMPLETED PHASE1

Imaging Regional Lung Defect Severity

NCT01640288

COPD

COMPLETED PHASE1/PHASE2

Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease)

NCT02719184

Pulmonary Disease, Chronic Obstructive Pulmonary Emphysema

COMPLETED

COPD-Related Physiology and the Brain

NCT03269721

Pulmonary Disease, Chronic Obstructive (COPD) Cognitive Impairment

COMPLETED

The Role of Quantitative CT and Radiomic Biomarkers for Precision Medicine in Pulmonary Fibrosis

NCT06323876

Idiopathic Pulmonary Fibrosis

RECRUITING

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Imaging-based metrics have recently played a central role in the quest to identify chronic obstructive pulmonary disease (COPD) phenotypes, serving to establish homogeneous sub-populations to aid in genotyping, therapeutic targeting and design and outcomes assessment. Recent findings in both animals and humans have lead us to believe that CT derived perfusion (PBF) and mean transit time (MTT) measures within regionally injured lung parenchyma provide for a functional phenotype of which may be directly tied to the etiology of the pathologic process leading to emphysema in acentrilobular emphysema susceptible subset of the smoking population. The primary hypotheses of the proposal are built around the notion that smokers prone to emphysema have abnormal vasoregulation in that regional hypoxic pulmonary vasoconstriction (HPV) continues despite regional lung injury. This failure to block vasoconstriction alters the repair response and leads to tissue destruction in emphysema susceptible smokers (SS) with abnormal vasoregulation. The normal response to regional hypoxia is to shunt blood towards better-ventilated regions. However, smoking induces small scale, regional infiltrates which in turn lead to local hypoxia, HPV would interfere with defense mechanisms serving to clear the irritant and thus interfere with mechanisms of repair. The investigators have demonstrated that, in SS subjects with normal PFTs but CT evidence of early centriacinar emphysema (CAE), there is an increased heterogeneity of perfusion. This is supportive of the notion that attenuation of vasoconstriction has failed. Further, the investigators have demonstrated a tight correlation between quantitative CT evidence of emphysema with reduced lung volume (LV) filling down to very small amounts of emphysema.

The investigators outline a series of experiments seeking to:

1. link increased pulmonary perfusion heterogeneity in SS subjects to the lung's response to alveolar oxygenation;
2. establish that the perfusion heterogeneity is reversible;
3. demonstrate that the response to inflammation and not just inflammation itself is a key factor in the increased heterogeneity.

With any combination of positive outcomes of this study, the investigators will have provided new insights into disease etiology, serving to provide new targets for disease intervention and providing the tools needed for assessing outcomes.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Emphysema

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sildenafil

40 subjects (20M and 20F) will be recruited to study non-contrast imaging at TLC and 20%VC and with contrast using DECT scans 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.

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

One dose of 20 mg Sildenafil will be given one hour before CT imaging.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sildenafil

One dose of 20 mg Sildenafil will be given one hour before CT imaging.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Revatio

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Must be between the ages of 25 and 65.
2. Must be currently smoking at least 1/2 pack/day (confirmed with cotinine level).
3. Must have pulmonary function test (PFT) results that meet the following (there will be two groups):

Group 1:
* Forced expiratory volume at one second (FEV1)/Forced vital capacity (FVC) \> 70%
* Forced Expiratory Flow at 25-75% of predicted(FEF25-75) \> 79% of predicted
* FVC greater than 80% of predicted

Group 2:

For subjects with mild lung impairment:
* FEV1\>80% of predicted
* FEV1/FVC\<0.7
4. Must be able to give informed consent for self.

Exclusion Criteria

1. Pregnant or breastfeeding females.
2. Body Mass Index (BMI) greater than 32.
3. Weight of greater than 220 pounds (100 kg).
4. Allergies to shell fish, seafood, eggs or iodine.
5. Heart disease, kidney disease or diabetes.
6. Diagnosis of asthma.
7. 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).
8. Any metal in or on the body between the nose and the abdomen.
9. Any major organ system disease (by judgment of study medical team).
10. A glomerular filtration rate of 60 cc per minute or less.

1. Nitroglycerin usage or nitrates (in addition to nitroglycerin) and use of phosphodiesterase 5 (PDE5) inhibitors within the previous 7 days of the study date.
2. Prior history of hypersensitivity to Sildenafil.

Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes