Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema
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|ClinicalTrials.gov Identifier: NCT02682147|
Recruitment Status : Recruiting
First Posted : February 15, 2016
Last Update Posted : October 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Emphysema||Drug: Sildenafil||Phase 4|
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:
- link increased pulmonary perfusion heterogeneity in SS subjects to the lung's response to alveolar oxygenation;
- establish that the perfusion heterogeneity is reversible;
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema|
|Actual Study Start Date :||July 10, 2017|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||December 2023|
No Intervention: Hypoxia study group
40 subjects will recruited to study normoxia compared to hypoxia and normoxia compared to hyperoxia. 20M and 20F subjects will be evaluated in each group under normoxia with low dose non-contrast CT at total lung capacity (TLC) and 20% vital capacity (VC) and then with contrast using dual energy CT to evaluate heterogeneity of perfused blood volume (PBV). Following the normixia scans, in 40 of the subjects hypoxia will be induced by breathing an inspired FIO2 of 15%. or hyperoxia will be induced by breathing an inspired FIO2 of 100%. During hypoxia or hyperoxia the non-contrast and PBV scans mentioned under normoxia will be repeated.
No Intervention: Hyperoxia Study Group
40 subjects will recruited to study normoxia compared to hypoxia and normoxia compared to hyperoxia. 20M and 20F subjects will be evaluated in each group under normoxia with low dose non-contrast CT at TLC and 20% vital capacity (VC) and then with contrast using dual energy CT to evaluate heterogeneity of perfused blood volume (PBV). Following the normixia scans, in 40 of the subjects hypoxia will be induced by breathing an fraction of inspired oxygen FIO2 of 15%. or hyperoxia will be induced by breathing an inspired FIO2 of 100%. During hypoxia or hyperoxia the non-contrast and PBV scans mentioned under normoxia will be repeated.
Experimental: PAV Study Group
40 subjects (20M and 20F) will be studied with non-contrast imaging at TLC and 20%VC and with contrast using DECT to assess PBV as above. Following these baseline studies, the subject will be taken to the clinical research unit and administered of 20 mg of Sildenafil and then the same scanning will be repeated one hour after sildenafil administration.
One dose of 20 mg Sildenafil will be given one hour before CT imaging
Other Name: Revatio
- Dual energy CT determined pulmonary blood volume will be measured in a total of 120 subjects before and after hyperoxia, hypoxia, and sildenafil. [ Time Frame: 5 years ]Our outcome measure is the change in regional blood volume between baseline and interventions with hypoxia, hyperoxia, and sildenafil.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02682147
|Contact: Debra J OConnell Moore, MBAemail@example.com|
|Contact: Sue E Salisbury, BSfirstname.lastname@example.org|
|United States, Iowa|
|University of Iowa||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Debra O'Connell-Moore, BS 319-356-1785 email@example.com|
|Contact: Ann Thompson 319-353-6213 firstname.lastname@example.org|
|Principal Investigator: Eric A Hoffman, Ph.D.|
|Principal Investigator:||Eric A Hoffman, PhD||University of Iowa|