Comparison of 129Xe MRI With 19F MRI in CF Lung Disease

NCT03482960 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 17-2569XePFP2017
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to compare the capabilities of two novel imaging techniques: polarized perfluorinated gas mixed with oxygen, and hyperpolarized xenon mixed with N2 to detect changes in lung ventilation using MRI.

Conditions

Cystic Fibrosis

Keywords

imaging; hyperpolarized; perfluorinated; MRI; lung

Outcome Measures

Primary Outcomes (1)

• Volume of unventilated lung area after a single 129Xe inhalation and after each inhalation cycle with PFP

  Primary comparison will be the VDP with Xenon (single breath) and after first PFP inhalation cycle (3 breaths of PFP)

  1 hour

Secondary Outcomes (3)

• Signal-to-noise (SNR) of each modality

  20 minutes

• Rate constant describing wash-in and wash-out of PFP

  15 minutes

• Correlation between VDP identified by each modality and spirometry and Lung Clearance Index (LCI)

  2 hours

Study Arms (2)

129Xe MRI

EXPERIMENTAL

Participants will self-administer hyperpolarized xenon gas via inhalation prior to the investigators acquiring MRI images. MRI imaging will be taken during approximately 15-second breath-holds. After the MRI is complete, participant performs spirometry maneuvers in a room outside the magnet. Once a minimum of 15 minutes has elapsed since leaving the MRI scanner, the participant will return to the MRI scanner, where the second phase of the study will occur. 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.

Drug: Hyperpolarized Xenon gas; Drug: PFP

19F MRI with PFP

EXPERIMENTAL

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. After the MRI is complete, participant performs spirometry maneuvers in a room outside the magnet. Once a minimum of 15 minutes has elapsed since leaving the MRI scanner, the participant returns to the MRI scanner, where he/she will self-administer hyperpolarized xenon gas prior to acquiring MRI images. MRI imaging will be taken during approximately 15-second breath-holds.

Drug: Hyperpolarized Xenon gas; Drug: PFP

Interventions

Hyperpolarized Xenon gas DRUG

Hyperpolarized Xenon gas * Hyperpolarized mixture (750ml HP 129Xe and 250ml nitrogen) * Administration: By mouthpiece attached to a single use Tedlar bag. * Dosage: 750 mL of the 129Xe mixture up to, but not exceeding, four doses of the 129Xe. * Frequency: 10-minute interval between doses.

Also known as: 129Xe

129Xe MRI; 19F MRI with PFP

PFP DRUG

* 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 the 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.

Also known as: Perfluoropropane gas (C3F8); 19F

129Xe MRI; 19F MRI with PFP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be at least 18 years of age;
• 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 forced expiratory volume in 1 second (FEV1) of \>15% from baseline over the preceding 4 weeks prior to enrollment
• Baseline FEV1 \>70% of predicted.
• 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
• Subjects must be willing and able to comply with scheduled visits and other trial procedures.
• Subjects must be at least 18 years of age;
• Non-smokers (\<10 pack year history and no active smoking in the past year);
• Baseline FEV1 \>70% of predicted.
• No use of supplemental oxygen or clinically significant lung disease
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial
• Subjects must be willing and able to comply with scheduled visits and other trial procedures.

You may not qualify if:

• Active or past smokers with less than 1 years since quitting or \>10 pack-year smoking history
• Co-existent asthma (as evidenced by either clinical diagnosis, chronic oral steroid use, or marked broncho-reactivity on pulmonary function testing)
• Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of contraindications including
• Occupation (past or present) of machinist, 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.)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• McCallister A, Chung SH, Antonacci M, Z Powell M, Ceppe AS, Donaldson SH, Lee YZ, Branca RT, Goralski JL. Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease. Magn Reson Med. 2021 Feb;85(2):1028-1038. doi: 10.1002/mrm.28457. Epub 2020 Aug 8.

  PMID: 32770779 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Jennifer Goralski, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: March 29, 2018
• Study Start: May 29, 2018
• Primary Completion: April 9, 2019
• Study Completion: April 10, 2019
• Last Updated: January 25, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)