- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02682147
Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Debra J OConnell Moore, MBA
- Phone Number: 319-356-1693
- Email: debra-oconnell-moore@uiowa.edu
Study Contact Backup
- Name: Sue E Salisbury, BS
- Phone Number: 319-356-1810
- Email: sue-salisbury@uiowa.edu
Study Locations
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- Recruiting
- University of Iowa
-
Contact:
- Debra O'Connell-Moore, BS
- Phone Number: 319-356-1785
- Email: debra-oconnell-moore@uiowa.edu
-
Contact:
- Ann Thompson
- Phone Number: 319-353-6213
- Email: ann-thompson@uiowa.edu
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Principal Investigator:
- Eric A Hoffman, Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must be between the ages of 25 and 65.
- 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 (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
- 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).
- A glomerular filtration rate of 60 cc per minute or less.
For the subjects that will receive Sildenafil as part of the study, additional exclusion criteria are as follows:
- Nitroglycerin usage or nitrates (in addition to nitroglycerin) and use of phosphodiesterase 5 (PDE5) inhibitors within the previous 7 days of the study date.
- Prior history of hypersensitivity to Sildenafil.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
scan completed after 5 minutes of breathing in hypoxic air
Other Names:
|
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.
|
scan completed after up to 15 minutes of breathing in hyperoxic air
Other Names:
|
Experimental: 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.
|
One dose of 20 mg Sildenafil will be given one hour before CT imaging.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Pre sildenafil adminstration and one hour after sildenafil adminstration.
|
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
|
Pre hyperoxic breathing and 15 minutes 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
|
Pre hypoxic breathing and 15 minutes post hypoxic breathing
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Eric A Hoffman, PhD, University of Iowa
Publications and helpful links
General Publications
- Alford SK, van Beek EJ, McLennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7485-90. doi: 10.1073/pnas.0913880107. Epub 2010 Apr 5.
- Iyer KS, Newell JD Jr, Jin D, Fuld MK, Saha PK, Hansdottir S, Hoffman EA. Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease. Am J Respir Crit Care Med. 2016 Mar 15;193(6):652-61. doi: 10.1164/rccm.201506-1196OC.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Disease Attributes
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Chronic Disease
- Pulmonary Emphysema
- Emphysema
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Sildenafil Citrate
Other Study ID Numbers
- 201508782
- R01HL130883 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
Study Data/Documents
-
Individual Participant Data Set
Information identifier: Data Distribution
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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