EmphysemaPhase 4NCT02682147
Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema
A Phase 4 study testing Sildenafil in people with Emphysema, run by Eric A. Hoffman at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Emphysema
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2017to May 2025
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Emphysema
- Being tested
- Sildenafil
- Medical subject headings
- Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Revatio
One dose of 20 mg Sildenafil will be given one hour before CT imaging.
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Experimental | 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. Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perfused blood volume assessed pre and post sildenafil administration in susceptible smoker (SS) subjects.
Regional heterogeneity perfused blood volume will be measured by duel energy CT scan at two time points and compared at two points, pre and post the administration of sildenafil.
Measured: Pre sildenafil adminstration and one hour after sildenafil adminstration.
Perfused blood volume assessed pre and post sildenafil administration in non-susceptible smoker (SS) subjects.
Regional heterogeneity perfused blood volume will be measured by duel energy CT scan at two time points and compared at two points, pre and post the administration of sildenafil.
Measured: Pre sildenafil adminstration and one hour after sildenafil adminstration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2016 (estimated)
- Study start10 Jul 2017
- Primary completionMay 2025 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eric A. Hoffman
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Eric A. Hoffman, University of Iowa
- Investigators
- Eric A Hoffman, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02682147
- Sponsor's protocol ID
- 201508782
- Other IDs
- R01HL130883
- Status last verified
- Apr 2025
- First submitted
- 12 Jan 2016
- Last updated
- 15 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: CT images will be shared including non-contrast images at TLC, FRC and RV as well as dual energy CT image data used to assess regional perfused blood volume. All associated pulmonary function test results will be shared. CT-derived metrics
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.
PubMed 20368443Iyer 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.
PubMed 26569033
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional CT Assessment of Pulmonary Arterial Dysfunction in Smoking Associated Emphysema
- ClinicalTrials.gov ID
- NCT02682147
- Acronym / sponsor ID
- 201508782
- Conditions
- Emphysema
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Eric A. HoffmanUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 10 Jul 2017 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 15 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Experimental | Drug: Sildenafil40 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. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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):
- Must be able to give informed consent for self.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: RevatioOne dose of 20 mg Sildenafil will be given one hour before CT imaging. | Drug | Sildenafil |
Primary outcome
Perfused blood volume assessed pre and post sildenafil administration in susceptible smoker (SS) subjects.
Time frame: Pre sildenafil adminstration and one hour after sildenafil adminstration.
Regional heterogeneity perfused blood volume will be measured by duel energy 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 sildenafil administration in non-susceptible smoker (SS) subjects.
Time frame: Pre sildenafil adminstration and one hour after sildenafil adminstration.
Regional heterogeneity perfused blood volume will be measured by duel energy CT scan at two time points and compared at two points, pre and post the administration of sildenafil.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2025.
- Results publication: PubMed 20368443Alford 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.
- Results publication: PubMed 26569033Iyer 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.
- Individual participant dataSharing planned: Yes. CT images will be shared including non-contrast images at TLC, FRC and RV as well as dual energy CT image data used to assess regional perfused blood volume. All associated pulmonary function test results will be shared. CT-derived metrics
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric A Hoffman, PhD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sildenafil in people with Emphysema, run by Eric A. Hoffman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perfused blood volume assessed pre and post sildenafil administration in susceptible smoker (SS) subjects. (time frame: Pre sildenafil adminstration and one hour after sildenafil adminstration.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02682147, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2025; AzTrials last refreshed its copy on 6 Nov 2026.