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 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Emphysema||Drug: Hypoxia administration study group Drug: Hyperoxia administration study group 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:||None (Open Label)|
|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|
Experimental: Hypoxia Administration study group
40 subjects will be recruited to study normoxia oxygen compared to hypoxia oxygen. 20M and 20F subjects will be evaluated under normoxia oxygen with low dose non-contrast CT scans at total lung capacity (TLC) and 20% vital capacity (VC) and then with contrast using dual energy CT scans to evaluate heterogeneity of perfused blood volume (PBV). For the intervention, following the normixia scans, hypoxia administration will be administered by breathing an inspired FIO2 of 15% oxygen and the non-contrast and contrast using DECT scans to evaluate heterogeneity of perfused blood volumen will be completed.
Drug: Hypoxia administration study group
scan completed after 5 minutes of breathing in hypoxic air
Other Name: Oxygen
Experimental: Hyperoxia Administration study group
40 subjects will recruited to study normoxia oxygen scans compared to hyperoxia scans. 20M and 20F subjects will be evaluated under normoxia with low dose non-contrast CT scans at TLC and 20% vital capacity (VC) and then with contrast scans using DECT to evaluate heterogeneity of perfused blood volume (PBV). For the intervention, following the normoxia scans, hyperoxia administration will be administered by breathing an inspired FIO2 of 100% oxygen and the non-contrast and contrast using DECT to evaluate heterogeneity of perfused blood volumen will be completed.
Drug: Hyperoxia administration study group
scan completed after up to 15 minutes of breathing in hyperoxic air
Other Name: Oxygen
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.
One dose of 20 mg Sildenafil will be given one hour before CT imaging.
Other Name: Revatio
- Perfused blood volume assessed pre and post sildenafil administration [ Time Frame: Pre sildenafil adminstration and one hour after sildenafil adminstration. ]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.
- Perfused blood volume assessed pre and post hyperoxic breathing [ Time Frame: Pre hyperoxic breathing and 15 minutes post hyperoxic breathing ]Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post hyperoxic breathing
- Perfused blood volume assessed pre and post hypoxic breathing [ Time Frame: Pre hypoxic breathing and 15 minutes post hypoxic breathing ]Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post hypoxic breathing
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, MBAfirstname.lastname@example.org|
|Contact: Sue E Salisbury, BSemail@example.com|
|United States, Iowa|
|University of Iowa||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Debra O'Connell-Moore, BS 319-356-1785 firstname.lastname@example.org|
|Contact: Ann Thompson 319-353-6213 email@example.com|
|Principal Investigator: Eric A Hoffman, Ph.D.|
|Principal Investigator:||Eric A Hoffman, PhD||University of Iowa|