Assessment of Lung Movement With CT in Healthy Subjects and Patients With ILD
Phase: NA
Conditions: Interstitial Lung Disease
Sponsor: University of Missouri-Columbia

 
 
 
Assessment of Lung Movement With Computed 
Tomography (CT) 
 
 
 
NCT03068091 
 
April 26, 2017 
 

MU IRB version:  3/26/2014 
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Date: _4/26/17___________________    
Version Number: __2________________ 
Principal Investigator: __Talissa Altes, MD _______________ 
Application Number: _2006114 
Application Title: Assessment of lung movement with CT in healthy subjects and Patients with ILD 
 
Clinical Trial Protocol 
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1. Abstract (problem, hypothesis and importance of research) 
 
Interstitial lung disease (ILD) is a group of lung disorders in which the lung tissues become 
inflamed and then damaged. Idiopathic Pulmonary Fibrosis (IPF) is one of the subtypes of ILD 
which has characteristic histological and CT features. It is well known that microscopic 
fibrosis occurs in the lungs of IPF patients well before the structural changes of fibrosis 
become apparent on CT. By combining sophisticated image analysis with CT scans obtained at 
full inspiration, full expiration, and possibly during breathing, it may be possible to detect 
earlier changes of IPF than currently possible by looking at macro structural features alone. 
With the recent development of new and costly therapeutics for IPF, early detection of the 
disease and improved monitoring of treatment efficacy will become important. Using CT to 
assess regional lung compliance has the potential to become an easily translated clinical tool. 
 
2. Objectives This is a pilot clinical trial to determine whether CT assessment of lung motion has 
the potential to be useful in the assessment of patients with ILD. 
 
3. Background  
 
In a prior research collaboration between the DoD and the University of Virginia, the airflow 
in healthy subjects and subjects with COPD was assessed using hyperpolarized gas MRI and 
CT imaging.  In this project, one of the healthy subjects was found to have early (subclinical) 
idiopathic pulmonary fibrosis (IPF).  Interestingly in this subject there was reduced lung 
motion on analysis of the CT in regions of the lung that are typically first affected by IPF but 
that still looked structurally nearly normal on CT. In a prior study, a correlation was found 
between honeycombing on CT (a classic feature of IPF) and pulmonary function tests (ref). In 
this project, we will assess lung motion on CT in both healthy subjects and patients with ILD 
to determine whether alterations of lung motion appear to precede alterations in lung 
structure (such as honeycombing) as seen on CT. 
 
Experience with procedures:  The pulmonary function testing and chest CT procedures will be 
completed according to the current clinical standards for the respective test.  
 
Drug/device: None 
 
 
4. Study Procedures 
a. Study design, including the sequence and timing of study procedures (distinguish 
research procedures from those that are part of routine care). 
 
20 subjects with Interstitial Lung Disease (ILD) and 20 age matched healthy normal 
subjects will be enrolled to undergo a non-contrast Chest CT and pulmonary function 

MU IRB version:  3/26/2014 
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testing (PFT). CT images will be collected with inspiration and expiration.  Additional 
low radiation dose images may be collected during breathing. The CT images will be 
analyzed and compared with PFT results. A urine pregnancy test will be obtained for 
subjects of childbearing potential. 
 
b. Study duration and number of study visits required of research participants. 
 
The CT and PFTs can be completed in one 2 to 3-hour session, but may be scheduled on 
different days depending on the subject and clinic schedule.  The CT scan takes 
approximately 10 minutes and the PFTs take approximately one hour.   
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. 
Not Applicable 
 
d. Justification of why participants will not receive routine care or will have current 
therapy stopped. 
Subject’s routine care will not be disrupted or stopped. 
 
e. Justification for inclusion of a placebo or non-treatment group. 
Not Applicable 
 
f. Definition of treatment failure or participant removal criteria. 
• If there is a concern for the participant’s health 
• If the participant’s underlying disease gets worse  
• The study sponsor closes the study for safety, administrative or other reasons   
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. 
Not Applicable 
 
5. Inclusion/Exclusion Criteria 
Inclusion Criteria: 
• Subjects with ILD: Subjects must have a physician diagnosis of ILD and be in stable 
pulmonary condition at the time of the CT 
• Healthy subjects: Subjects must have no history of pulmonary disease and smoked less 
than 100 cigarettes in their lifetime.   
 
Exclusion Criteria:   
• Subjects less than 18 years of age 
 
 
6. Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used. 
Not Applicable 
 
b. Justification and safety information if FDA approved drugs will be administered for 
non-FDA approved indications or if doses or routes of administration or participant 
populations are changed. 
Not Applicable 
 

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c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.  
Not Applicable 
 
 
 
7. Study Statistics 
a. Primary outcome variable. This is a pilot study to determine whether alteration lung 
motion on CT may be an early indicator of ILD. We will assess the change in lung 
volume on CT from inspiration to expiration on a lobar basis.  
b. Secondary outcome variables. A radiologist reader will assess the severity of structural 
changes in the lung on a lobar basis.  Pulmonary function testing will also be performed 
(FEV1, FVC)  
c. Statistical plan including sample size justification and interim data analysis. The lung 
motion, structural severity score and pulmonary function tests will be compared using 
a Spearmen correlation coefficient.  As a small pilot study, we do not anticipate that 
any of the correlations will achieve statistical significance. The sample size was based 
on prior experience. No power calculation was performed as this is just a pilot study to 
determine whether this technique may warrant further study. The results from this 
study may be used to power a future study. 
d. Early stopping rules. None 
 
8. Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected 
frequency. 
 
Risk of CT: The CT performed as part of the study is the same as a clinical CT scan.  The 
total effective radiation dose a subject will receive from the CT study is approximately 
7 mSv. For comparison, the dose from the CT is roughly 15% the annual radiation dose 
safely allowed for a radiation worker such as the person performing the CT scan. The 
precise risk from this dose is not known but is thought to be small.  
 
Risk of PFT:  Since pulmonary function testing requires blowing hard several times, the 
subject may cough or feel short of breath during or after the test.   
 
b. Steps taken to minimize the risks.  The CT parameters will be selected to achieve an 
appropriate balance between image quality and radiation dose and will be similar to 
the multicenter NIH funded COPD Gene trial CT scans. 
 
c. Plan for reporting unanticipated problems or study deviations. 
All unanticipated problems and deviations will be reported to the IRB within 5 
business days of first learning of the event. 
 
d. Legal risks such as the risks that would be associated with breach of confidentiality. 
Unanticipated problems will be reported on the IRB event report within 5 days of 
learning of the event. 
 
e. Financial risks to the participants. 
None 
 
9. Benefits 

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a. Description of the probable benefits for the participant and for society. 
 
There are no direct benefits to the subject. This study may improve our understanding 
of alterations in lung compliance in patients with ILD.  One potential offshoot of this 
study would be to assess whether alterations in lung compliance are an early indicator 
of response (or lack thereof) to treatments for ILD. Thus this study has the potential to 
benefit ILD patients in the future. 
 
 
 
10. Payment and Remuneration 
a. Detail compensation for participants including possible total compensation, proposed 
bonus, and any proposed reductions or penalties for not completing the protocol. 
Subjects will be paid $75 for CT and $25 for PFT.   
 
In addition, for the healthy subjects, if the study CT indicates that a follow up CT is 
required, the follow up CT will be covered by study funds. 
 
11. Costs 
a. Detail costs of study procedure(s) or drug (s) or substance(s) to participants and 
identify who will pay for them. 
There are no costs to participants for participating in the study.  All study costs will be paid 
for by the sponsor. 
 
12. References 
 
a. List of references supporting research question.  
 
Nakagawa H, Nagatani Y, Takahashi 3, Ogawa E, Tho NV, Ryujin Y, Nagao 1, Nakano 
Y,.Quantitative CT analysis of honeycombing area in idiopathic pulmonary fibrosis: 
Correlations with pulmonary function tests. Eur J Radiol. 2016 Jan;85(1):125-30. doi: 
10.1016/j.ejrad.2015.11.011.  
 
13. Data Sharing 
 
Study data, including demographic information and imaging and pulmonary function test 
results collected by the University of Missouri will be shared with the Biotechnology High 
Performance Computing Software Applications Institute (BHSAI), a subordinate of the 
Telemedicine and Advance Technology Research Center (TATRC), which is part of the U.S. 
Army Medical Research and Materiel Command (MRMC) at Fort Detrick, Frederick, 
Maryland. Only investigators at the University of Missouri will have access to the codes 
that could be used to identify individual subjects. In all instances, data and images sent to 
collaborators will contain a code for each subject, and will not contain any subject PHI that 
could link the information to an individual subject enrolled at the University of Missouri. 
Data shared with the above research collaborators will be used for this study and possibly 
for future studies related to lung function or lung disease.