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Trial record 24 of 525 for:    Emphysema

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
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Eric A. Hoffman, University of Iowa

Brief 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. 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

Condition or disease Intervention/treatment Phase
Emphysema Drug: Sildenafil Phase 4

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:

  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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Emphysema Smoking

Arm Intervention/treatment
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.
Drug: Sildenafil
One dose of 20 mg Sildenafil will be given one hour before CT imaging
Other Name: Revatio




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

For the subjects that will receive Sildenafil as part of the study, additional exclusion criteria are as follows:

  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.

Information from the National Library of Medicine

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


Contacts
Contact: Debra J OConnell Moore, MBA 319-356-1693 debra-oconnell-moore@uiowa.edu
Contact: Sue E Salisbury, BS 319-356-1810 sue-salisbury@uiowa.edu

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Debra O'Connell-Moore, BS    319-356-1785    debra-oconnell-moore@uiowa.edu   
Contact: Ann Thompson    319-353-6213    ann-thompson@uiowa.edu   
Principal Investigator: Eric A Hoffman, Ph.D.         
Sponsors and Collaborators
Eric A. Hoffman
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Eric A Hoffman, PhD University of Iowa

Responsible Party: Eric A. Hoffman, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT02682147     History of Changes
Other Study ID Numbers: 201508782
R01HL130883 ( U.S. NIH Grant/Contract )
First Posted: February 15, 2016    Key Record Dates
Last Update Posted: October 23, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Emphysema
Pulmonary Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents