Back to resultsXenon MRI and Progressive ILD
Primary Purpose
Idiopathic Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized 129 Xenon Gas Comparing Progressive Pulmonary Fibrosis Treatment
Sponsored by
About this trial
This is an interventional diagnostic trial for Idiopathic Pulmonary Fibrosis focused on measuring Magnetic Resonance Imaging
Eligibility Criteria
Inclusion Criteria:
We will include all patients who are over 18 years of age with a physician-diagnosed ILD of one of the below subtypes based on multidisciplinary consensus
- Chronic hypersensitivity pneumonitis
- Autoimmune interstitial lung disease (including rheumatoid arthritis-ILD, mixed connective tissue disorder related ILD, myositis related ILD, scleroderma related ILD, and idiopathic pneumonia with autoimmune features)
- Idiopathic NSIP
- Unclassifiable idiopathic interstitial pneumonia
- Fibrotic lung disease affecting more than 10% of lung volume on high-resolution CT, per Duke radiology review
Evidence of any of the following criteria for progression of ILD within the 24 months before screening:
- Relative decline in FVC % predicted of at least 10%
- Relative decline in FVC % predicted ≥ 5% - < 10 combined with either increasing extent of fibrotic changes on HRCT or worsening of respiratory symptoms
- Worsening respiratory symptoms and increased extent of fibrosis on HRCT
- Willing and able to give informed consent and adhere to visit/protocol schedules
- Immunosuppressive medication, including azathioprine, cyclosporine, mycophenolate mofetil, rituximab, cyclophosphamide, or oral glucocorticoids are permitted at the discretion of the treating physician
Exclusion Criteria:
- Subject is less than 18 years of age
- Prior treatment with nintedanib or pirfenidone
- Subject is pregnant or lactating
- Prior investigational drug use within 28 days
- MRI is contraindicated based on responses to MRI screening questionnaire
- Respiratory illness of a bacterial or viral etiology within 30 days of MRI
- Acute exacerbation within 30 days of MRI, defined by acute increases in oxygen requirement, bilateral alveolar filling opacities on imaging, and the need for antibiotics and/or systemic steroids
- Subject does not fit into 129Xe vest coil used for MRI
- Subject with ventricular cardiac arrhythmia in the past 30 days.
- Subject has history of cardiac arrest within the last year
- Subject deemed unlikely to be able to comply with instructions during imaging
- Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
Sites / Locations
- Duke UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Progressive Pulmonary Fibrosis
Arm Description
Whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Progressive Pulmonary Fibrosis patients receiving approved treatments.
Outcomes
Primary Outcome Measures
Change in 129Xe MRI barrier uptake 3 months after anti-fibrotic initiation
The outcome will assess changes in 129Xe MRI barrier uptake 3 months after nintedanib initiation.
Secondary Outcome Measures
Change in 129Xe MRI barrier uptake 6 months after anti-fibrotic initiation
The outcome will assess changes in 129Xe MRI barrier uptake 6 months after nintedanib initiation.
Change in 129Xe MRI RBC to barrier ratio 3 months after anti-fibrotic initiation
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value
Change in 129Xe MRI RBC to barrier ratio 6 months after anti-fibrotic initiation
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with elevated barrier uptake at baseline greater than 2 standard deviations of a healthy reference cohort
Time to disease progression will be recorded in months
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with decreased RBC transfer at baseline, lower than 2 standard deviations of a healthy reference cohort
Time to disease progression will be recorded in months
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with a reduced RBC to barrier ratio, greater than 2 standard deviations of a healthy reference cohort
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value. Time to disease progression will be recorded in months
Time to acute exacerbation or respiratory hospitalization in individuals with elevated barrier uptake at baseline greater than 2 standard deviations of a healthy reference cohort
Time to acute exacerbation or respiratory hospitalization will be an aggregate value and will be recorded in months
Time to acute exacerbation or respiratory hospitalization in individuals with decreased RBC transfer at baseline, lower than 2 standard deviations of a healthy reference cohort
Time to acute exacerbation or respiratory hospitalization will be an aggregate value and will be recorded in months
Full Information
NCT ID
NCT05241275
First Posted
February 3, 2022
Last Updated
December 15, 2022
Sponsor
Duke University
Collaborators
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT05241275
Brief Title
Xenon MRI and Progressive ILD
Official Title
XENON ILD: 129Xe MRI to Evaluate aNtifibrotic respOnse and progressioN in ILD
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 19, 2022 (Actual)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
June 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Duke University
Collaborators
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The XENON ILD study is a single arm, un-blinded study at Duke University enrolling patients with non-idiopathic pulmonary fibrosis (IPF) progressive fibrosis (PF) interstitial lung disease (ILD). Patients who meet criteria for ILD-progression (defined below in inclusion/exclusion criteria) will be consented prior to the initiation of anti-fibrotic therapy. Subjects will undergo an approximately hour long comprehensive MRI protocol, including administration of multiple doses of hyperpolarized 129Xe. The subjects will have this initial study prior to initiation of anti-fibrotic therapies and repeat MRI studies at 3, 6 and 12 months following the initiation of therapy. If subjects do not decide to initiate anti-fibrotic therapy per discussion with their physician, then the 3, 6 and 12 months repeat studies will initiate based on time after enrollment.
Detailed Description
The XENON ILD study is a single arm, un-blinded study at Duke University enrolling patients with non-IPF PF-ILD. Patients who meet criteria for ILD-progression (defined below in inclusion/exclusion criteria) will be consented prior to the initiation of anti-fibrotic therapy. Subjects will undergo an approximately hour long comprehensive MRI protocol, including administration of multiple doses of hyperpolarized 129Xe. The subjects will have this initial study prior to initiation of anti-fibrotic therapies and repeat MRI studies at 3, 6 and 12 months following the initiation of therapy. If subjects do not decide to initiate anti-fibrotic therapy per discussion with their physician, then the 3, 6 and 12 months repeat studies will initiate based on time after enrollment. We plan to consent 75 subjects with PF-ILD who are candidates for anti-fibrotic therapy to slow ILD progression. We will ensure that the study will include at least 38 subjects who start anti-fibrotic therapy after baseline first MRI scan and continue the therapy until his/her 3 month repeat MRI scan. This will be obtained by a pre-specified increase in the number of subjects until the 38 subject criteria is completed. Subject will not be excluded from the study due to stopping anti-fibrotic therapy for any reason during the study.
Additional studies including pulmonary function studies, plasma and serum for biomarkers, whole blood for DNA (baseline visit only), whole blood for RNA, exhaled breath for biomarkers, 6 minute walk distance and a HRCT (only at the screening visit, 6 month visit, and 12 month visit) will be performed to determine how 129Xe MRI performs relative to standard of care evaluations for PF-ILD patients. Finally, following the study visits the research team will prospectively follow the patients' clinical course through periodic reviews of the medical record.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Keywords
Magnetic Resonance Imaging
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Progressive Pulmonary Fibrosis
Arm Type
Experimental
Arm Description
Whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Progressive Pulmonary Fibrosis patients receiving approved treatments.
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized 129 Xenon Gas Comparing Progressive Pulmonary Fibrosis Treatment
Intervention Description
Whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Progressive Pulmonary Fibrosis
Primary Outcome Measure Information:
Title
Change in 129Xe MRI barrier uptake 3 months after anti-fibrotic initiation
Description
The outcome will assess changes in 129Xe MRI barrier uptake 3 months after nintedanib initiation.
Time Frame
Baseline, 3 months
Secondary Outcome Measure Information:
Title
Change in 129Xe MRI barrier uptake 6 months after anti-fibrotic initiation
Description
The outcome will assess changes in 129Xe MRI barrier uptake 6 months after nintedanib initiation.
Time Frame
Baseline and 6 months
Title
Change in 129Xe MRI RBC to barrier ratio 3 months after anti-fibrotic initiation
Description
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value
Time Frame
Baseline and 3 months
Title
Change in 129Xe MRI RBC to barrier ratio 6 months after anti-fibrotic initiation
Description
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value
Time Frame
Baseline and 6 months
Title
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with elevated barrier uptake at baseline greater than 2 standard deviations of a healthy reference cohort
Description
Time to disease progression will be recorded in months
Time Frame
Up to 12 months
Title
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with decreased RBC transfer at baseline, lower than 2 standard deviations of a healthy reference cohort
Description
Time to disease progression will be recorded in months
Time Frame
Up to 12 months
Title
Time to disease progression (occurrence of a ≥ 10% drop in percent predicted FVC, all cause death, or lung transplant) in individuals with a reduced RBC to barrier ratio, greater than 2 standard deviations of a healthy reference cohort
Description
RBC to barrier ratio is a ratio of the RBC transfer and barrier values and is reported as a single value. Time to disease progression will be recorded in months
Time Frame
Up to 12 months
Title
Time to acute exacerbation or respiratory hospitalization in individuals with elevated barrier uptake at baseline greater than 2 standard deviations of a healthy reference cohort
Description
Time to acute exacerbation or respiratory hospitalization will be an aggregate value and will be recorded in months
Time Frame
Up to 12 months
Title
Time to acute exacerbation or respiratory hospitalization in individuals with decreased RBC transfer at baseline, lower than 2 standard deviations of a healthy reference cohort
Description
Time to acute exacerbation or respiratory hospitalization will be an aggregate value and will be recorded in months
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
We will include all patients who are over 18 years of age with a physician-diagnosed ILD of one of the below subtypes based on multidisciplinary consensus
Chronic hypersensitivity pneumonitis
Autoimmune interstitial lung disease (including rheumatoid arthritis-ILD, mixed connective tissue disorder related ILD, myositis related ILD, scleroderma related ILD, and idiopathic pneumonia with autoimmune features)
Idiopathic NSIP
Unclassifiable idiopathic interstitial pneumonia
Fibrotic lung disease affecting more than 10% of lung volume on high-resolution CT, per Duke radiology review
Evidence of any of the following criteria for progression of ILD within the 24 months before screening:
Relative decline in FVC % predicted of at least 10%
Relative decline in FVC % predicted ≥ 5% - < 10 combined with either increasing extent of fibrotic changes on HRCT or worsening of respiratory symptoms
Worsening respiratory symptoms and increased extent of fibrosis on HRCT
Willing and able to give informed consent and adhere to visit/protocol schedules
Immunosuppressive medication, including azathioprine, cyclosporine, mycophenolate mofetil, rituximab, cyclophosphamide, or oral glucocorticoids are permitted at the discretion of the treating physician
Exclusion Criteria:
Subject is less than 18 years of age
Prior treatment with nintedanib or pirfenidone
Subject is pregnant or lactating
Prior investigational drug use within 28 days
MRI is contraindicated based on responses to MRI screening questionnaire
Respiratory illness of a bacterial or viral etiology within 30 days of MRI
Acute exacerbation within 30 days of MRI, defined by acute increases in oxygen requirement, bilateral alveolar filling opacities on imaging, and the need for antibiotics and/or systemic steroids
Subject does not fit into 129Xe vest coil used for MRI
Subject with ventricular cardiac arrhythmia in the past 30 days.
Subject has history of cardiac arrest within the last year
Subject deemed unlikely to be able to comply with instructions during imaging
Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia Salazar
Phone
9196602026
Email
claudia.salazar@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert M Tighe, MD
Organizational Affiliation
Duke University Health Systems
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Kummerer
Phone
919-283-2455
12. IPD Sharing Statement
Plan to Share IPD
No
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Xenon MRI and Progressive ILD
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