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19F MRI to Evaluate Regional Ventilation in Healthy Subjects and Subjects With Cystic Fibrosis

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
PFP
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cystic Fibrosis focused on measuring Lung, Imaging, Hyperpolarized, Perfluorinated, MRI

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for Healthy Participants:

  • Non-smokers (<10 pack-year history, and no active smoking in last 1 year);
  • No evidence of prior lung disease or lung injury by medical history, physical exam, and/or spirometry testing;
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
  • Participants must be willing and able to comply with scheduled visits and other trial procedures.

Exclusion Criteria for Healthy Participants:

  • Active or past smokers with less than 1 years since quitting or >10 pack-year smoking history

  • Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of contraindications including

    1. Occupation (past or present) of machiner, welder, grinder;
    2. Injury to the eye involving a metallic object
    3. Injury to the body by a metallic object (bullet, BB, shrapnel)
    4. Presence of a cardiac pacemaker or defibrillator
    5. Presence of aneurysm clips
    6. Presence of carotid artery vascular clamp
    7. Presence of neurostimulator
    8. Presence of insulin or infusion pump
    9. Presence of implanted drug infusion device that is not known to be MRI compatible (i.e., was placed outside of UNCH or is older than 10 years)
    10. Bone growth or fusion simulator
    11. Presence of cochlear, otologic or ear implant
    12. Any type of prosthesis (eye, penile, etc.)
    13. Artificial limb or joint
    14. Non-removable electrodes (on body, head or brain)
    15. Intravascular stents, filters or coils
    16. Shunt (spinal or intraventricular)
    17. Swan-ganz catheter
    18. Any implant held in place by a magnet
    19. Transdermal delivery system (e.g. Nitro)
    20. IUD or diaphragm
    21. Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface area
    22. Body piercings (MUST BE REMOVED BEFORE MRI)
    23. Any metal fragments
    24. Internal pacing wires
    25. Metal or wire mesh implants
    26. Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb. Claustrophobia
  • Unable to tolerate inhalation of gas mixture
  • Participation in a clinical trial with a study drug that may impact lung function in the past 14 days
  • Other severe acute or chronic medical or psychiatric condition or clinical laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial.
  • Pregnancy: women of childbearing potential must have a confirmed negative urine pregnancy test on the day of the MR scan, prior to the MRI scan.

Inclusion Criteria for CF Participants:

  • Non-smokers (<10 pack year history and no active smoking in the past year;
  • Diagnosis of cystic fibrosis as via standard sweat chloride/phenotypic features/genotyping
  • Stable lung disease as evidenced by no change in respiratory medications or change in FEV1 of >15% from baseline over the preceding 4 weeks prior to enrollment
  • Baseline FEV1 >30% of predicted. Roughly equivalent numbers of CF subjects with mild FEV1 >80% of predicted), moderate (FEV1 50-80% of predicted) and severe (FEV1 <50% of predicted) will be targeted for enrollment.
  • No use of supplemental oxygen
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
  • Participants must be willing and able to comply with scheduled visits and other trial procedures.

Exclusion Criteria for CF Participants:

  • Active or past smokers with less than 1 years since quitting or >10 pack-year smoking history
  • Active asthma flare, as perceived by the study physician or unstable asthma characterized by advancement of asthma therapy in the last month or two courses of oral steroids in the past six months.

  • Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of contraindications including

    1. Occupation (past or present) of machiner, welder, grinder;
    2. Injury to the eye involving a metallic object
    3. Injury to the body by a metallic object (bullet, BB, shrapnel)
    4. Presence of a cardiac pacemaker or defibrillator
    5. Presence of aneurysm clips
    6. Presence of carotid artery vascular clamp
    7. Presence of neurostimulator
    8. Presence of insulin or infusion pump
    9. Presence of implanted drug infusion device that is not known to be MRI compatible (i.e., was placed outside of UNCH or is older than 10 years)
    10. Bone growth or fusion simulator
    11. Presence of cochlear, otologic or ear implant
    12. Any type of prosthesis (eye, penile, etc.)
    13. Artificial limb or joint
    14. Non-removable electrodes (on body, head or brain)
    15. Intravascular stents, filters or coils
    16. Shunt (spinal or intraventricular)
    17. Swan-ganz catheter
    18. Any implant held in place by a magnet
    19. Transdermal delivery system (e.g. Nitro)
    20. IUD or diaphragm
    21. Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface area
    22. Body piercings (MUST BE REMOVED BEFORE MRI)
    23. Any metal fragments
    24. Internal pacing wires
    25. Metal or wire mesh implants
    26. Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb. Claustrophobia
  • Unable to tolerate inhalation of gas mixture
  • Participation in a clinical trial with a study drug that may impact lung function in the past 14 days
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial.
  • Pregnancy; women of childbearing potential must have a confirmed negative urine pregnancy test on the day of the MR scan, prior to the MRI scan.

Sites / Locations

  • The University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

19F MRI with PFP

Arm Description

PFP gas will be administered using a full-face mask during the MRI. Images are acquired during 12-second breath-hold after every 3rd breath. Before and after the MRI is complete, participants will perform spirometry maneuvers in a room outside of the magnet.

Outcomes

Primary Outcome Measures

Obtain technically sufficient 19F MRI images
Determine if 19F gas images of the human lung and airways can be obtained in both single breath-hold and gated breathing imaging studies with adequate signal level and image contrast to extract regional lung ventilation information.

Secondary Outcome Measures

Determine the reproducibility of ventilation assessments in the adult cystic fibrosis (CF) population.
Repeated scans will be optional for CF participants in order to begin to understand the repeatability of this outcome measure
Compare quantitative and qualitative image measures of lung ventilation using 19F MRI imaging to spirometric values.
Pair 19F lung images and Ventilation Defect Percentages with FEV1 obtained via spirometry

Full Information

First Posted
March 29, 2018
Last Updated
October 3, 2019
Sponsor
University of North Carolina, Chapel Hill
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1. Study Identification

Unique Protocol Identification Number
NCT03489590
Brief Title
19F MRI to Evaluate Regional Ventilation in Healthy Subjects and Subjects With Cystic Fibrosis
Official Title
19F Magnetic Resonance Imaging to Evaluate Regional Ventilation in Healthy Subjects and Subjects With Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
An open label non-randomized study enrolling up to 20 healthy participants and up to 30 participants with cystic fibrosis to establish a healthy versus disease comparison. Each participant will receive a mixture of inert gas (perfluoropropane (PFP)) in a ratio of 79% PFP to 21% oxygen as a contrast agent to enhance visualization of the airway and alveolar spaces using magnetic resonance imaging of inert gas/oxygen mixtures. The study consists of a screening visit followed by up to 2 study visits.
Detailed Description
The goal of this study is to evaluate the ability of conventional 'thermally' polarized perfluorinated gases (19F) mixed with oxygen to detect changes in ventilation using magnetic resonance imaging (MRI). A secondary goal is to assess the repeatability and the within-subject variability of these findings in CF lung disease. This is an open label pilot study expanding on work by other investigators currently using this technique in human subjects. Projection images using controlled breathing techniques will be obtained using 19F MRI, correlating spirometric variables with regional distribution of the gases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Lung, Imaging, Hyperpolarized, Perfluorinated, MRI

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This study enrolls both healthy volunteers and volunteers with cystic fibrosis. Both healthy and CF participants will receive the same treatment throughout the entirety of the study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
19F MRI with PFP
Arm Type
Experimental
Arm Description
PFP gas will be administered using a full-face mask during the MRI. Images are acquired during 12-second breath-hold after every 3rd breath. Before and after the MRI is complete, participants will perform spirometry maneuvers in a room outside of the magnet.
Intervention Type
Drug
Intervention Name(s)
PFP
Other Intervention Name(s)
Perfluoropropane gas (C3F8); 19F
Intervention Description
Composition: inhaled PFP, a gaseous contrast agent (79% PFP, 21% O2, pre-mixed, medical grade gas) Administration: Full-face disposable ventilation mask and a standard Douglas Bag system. Dosage: Two controlled breaths of contrast gas followed by a full breath and a 12-second breath-hold and scan for image acquisition. Frequency: Repeated 5 times followed by an identical five cycles with room air to ensure PFP gas wash-out has occurred.
Primary Outcome Measure Information:
Title
Obtain technically sufficient 19F MRI images
Description
Determine if 19F gas images of the human lung and airways can be obtained in both single breath-hold and gated breathing imaging studies with adequate signal level and image contrast to extract regional lung ventilation information.
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Determine the reproducibility of ventilation assessments in the adult cystic fibrosis (CF) population.
Description
Repeated scans will be optional for CF participants in order to begin to understand the repeatability of this outcome measure
Time Frame
1 week
Title
Compare quantitative and qualitative image measures of lung ventilation using 19F MRI imaging to spirometric values.
Description
Pair 19F lung images and Ventilation Defect Percentages with FEV1 obtained via spirometry
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for Healthy Participants: Non-smokers (<10 pack-year history, and no active smoking in last 1 year); No evidence of prior lung disease or lung injury by medical history, physical exam, and/or spirometry testing; Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. Participants must be willing and able to comply with scheduled visits and other trial procedures. Exclusion Criteria for Healthy Participants: Active or past smokers with less than 1 years since quitting or >10 pack-year smoking history Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of contraindications including Occupation (past or present) of machiner, welder, grinder; Injury to the eye involving a metallic object Injury to the body by a metallic object (bullet, BB, shrapnel) Presence of a cardiac pacemaker or defibrillator Presence of aneurysm clips Presence of carotid artery vascular clamp Presence of neurostimulator Presence of insulin or infusion pump Presence of implanted drug infusion device that is not known to be MRI compatible (i.e., was placed outside of UNCH or is older than 10 years) Bone growth or fusion simulator Presence of cochlear, otologic or ear implant Any type of prosthesis (eye, penile, etc.) Artificial limb or joint Non-removable electrodes (on body, head or brain) Intravascular stents, filters or coils Shunt (spinal or intraventricular) Swan-ganz catheter Any implant held in place by a magnet Transdermal delivery system (e.g. Nitro) IUD or diaphragm Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface area Body piercings (MUST BE REMOVED BEFORE MRI) Any metal fragments Internal pacing wires Metal or wire mesh implants Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb. Claustrophobia Unable to tolerate inhalation of gas mixture Participation in a clinical trial with a study drug that may impact lung function in the past 14 days Other severe acute or chronic medical or psychiatric condition or clinical laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial. Pregnancy: women of childbearing potential must have a confirmed negative urine pregnancy test on the day of the MR scan, prior to the MRI scan. Inclusion Criteria for CF Participants: Non-smokers (<10 pack year history and no active smoking in the past year; Diagnosis of cystic fibrosis as via standard sweat chloride/phenotypic features/genotyping Stable lung disease as evidenced by no change in respiratory medications or change in FEV1 of >15% from baseline over the preceding 4 weeks prior to enrollment Baseline FEV1 >30% of predicted. Roughly equivalent numbers of CF subjects with mild FEV1 >80% of predicted), moderate (FEV1 50-80% of predicted) and severe (FEV1 <50% of predicted) will be targeted for enrollment. No use of supplemental oxygen Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. Participants must be willing and able to comply with scheduled visits and other trial procedures. Exclusion Criteria for CF Participants: Active or past smokers with less than 1 years since quitting or >10 pack-year smoking history Active asthma flare, as perceived by the study physician or unstable asthma characterized by advancement of asthma therapy in the last month or two courses of oral steroids in the past six months. Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of contraindications including Occupation (past or present) of machiner, welder, grinder; Injury to the eye involving a metallic object Injury to the body by a metallic object (bullet, BB, shrapnel) Presence of a cardiac pacemaker or defibrillator Presence of aneurysm clips Presence of carotid artery vascular clamp Presence of neurostimulator Presence of insulin or infusion pump Presence of implanted drug infusion device that is not known to be MRI compatible (i.e., was placed outside of UNCH or is older than 10 years) Bone growth or fusion simulator Presence of cochlear, otologic or ear implant Any type of prosthesis (eye, penile, etc.) Artificial limb or joint Non-removable electrodes (on body, head or brain) Intravascular stents, filters or coils Shunt (spinal or intraventricular) Swan-ganz catheter Any implant held in place by a magnet Transdermal delivery system (e.g. Nitro) IUD or diaphragm Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface area Body piercings (MUST BE REMOVED BEFORE MRI) Any metal fragments Internal pacing wires Metal or wire mesh implants Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb. Claustrophobia Unable to tolerate inhalation of gas mixture Participation in a clinical trial with a study drug that may impact lung function in the past 14 days Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial. Pregnancy; women of childbearing potential must have a confirmed negative urine pregnancy test on the day of the MR scan, prior to the MRI scan.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer L Goralski, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23985278
Citation
Couch MJ, Ball IK, Li T, Fox MS, Littlefield SL, Biman B, Albert MS. Pulmonary ultrashort echo time 19F MR imaging with inhaled fluorinated gas mixtures in healthy volunteers: feasibility. Radiology. 2013 Dec;269(3):903-9. doi: 10.1148/radiol.13130609. Epub 2013 Oct 28.
Results Reference
background
PubMed Identifier
23722696
Citation
Halaweish AF, Moon RE, Foster WM, Soher BJ, McAdams HP, MacFall JR, Ainslie MD, MacIntyre NR, Charles HC. Perfluoropropane gas as a magnetic resonance lung imaging contrast agent in humans. Chest. 2013 Oct;144(4):1300-1310. doi: 10.1378/chest.12-2597.
Results Reference
background
PubMed Identifier
31855577
Citation
Goralski JL, Chung SH, Glass TM, Ceppe AS, Akinnagbe-Zusterzeel EO, Trimble AT, Boucher RC, Soher BJ, Charles HC, Donaldson SH, Lee YZ. Dynamic perfluorinated gas MRI reveals abnormal ventilation despite normal FEV1 in cystic fibrosis. JCI Insight. 2020 Jan 30;5(2):e133400. doi: 10.1172/jci.insight.133400.
Results Reference
derived

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19F MRI to Evaluate Regional Ventilation in Healthy Subjects and Subjects With Cystic Fibrosis

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