19F MRI of Ventilation in Subjects With Cystic Fibrosis Undergoing Treatment for Pulmonary Exacerbation

NCT03497117 | Terminated Early Phase 1 FDA Drug

• 2 other identifiers: 15-02392P30DK065988-11
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to use perfluorinated gas imaging to highlight regions of functional variation within the lungs of participants with cystic fibrosis (CF), and to correlate this with changes in spirometry, lung clearance index, and quality of life of CF subjects undergoing treatment for a pulmonary exacerbation.

Conditions

Cystic Fibrosis

Keywords

imaging; hyperpolarized; perfluorinated; MRI; lung; multiple breath washout; lung clearance index

Outcome Measures

Primary Outcomes (1)

• Whole lung ventilation defect volume (VDV)

  To obtain ventilation defect volumes (VDVs), investigators will use the final wash-in image to identify all regions of interest having a signal intensity below the pre-defined threshold which indicates poor ventilation. The combined volume of all these 'ventilation defect' regions will be computed to obtain the VDV.

  1 day

Secondary Outcomes (3)

• The wash-in kinetics of PFP

  1 day

• Ventilation defect percent (VDP) correlation with LCI

  1 day

• Ventilation defect percent (VDP) correlation with FEV1

  1 day

Study Arms (1)

CF pulmonary exacerbation group

OTHER

Patients with cystic fibrosis being treated for a pulmonary exacerbation will undergo Lung Clearance Index (LCI) and an MRI with PFP. LCI testing will take place before the MRI. Each test will take 5-20 minutes and up to three tests will be performed with at least 5-minute rest periods between each test. 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.

Device: Lung Clearance Index; Drug: MRI with PFP

Interventions

Lung Clearance Index DEVICE

To assess the efficiency of ventilation distribution and gas mixing by measuring the rate of clearance of an inert gas (nitrogen) from the lungs.

Also known as: LCI

CF pulmonary exacerbation group

MRI with PFP DRUG

* Description: 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.

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

CF pulmonary exacerbation group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-smokers (\<10 pack year history and no active smoking in the past year);
• Diagnosis of cystic fibrosis via standard sweat chloride/phenotypic features/genotyping
• Able to reproducibly perform lung function testing and have an FEV1 \>30% of predicted at screening.
• No requirement for 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.
• Diagnosis of a pulmonary exacerbation according to Fuchs criteria (4 of the following 12 signs and symptoms) deemed to require antibiotic treatment, and must also include the change in lung function criterion:
• Change in sputum
• New or increased hemoptysis
• Increased cough
• Increased dyspnea
• Malaise, fatigue, or lethargy
• Temperature above 38deg C
• Anorexia or weight loss
• Sinus pain or tenderness

You may not qualify if:

• Under 18 years of age
• Active or former 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 of 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 University of North Carolina Hospitals (UNCH) or is older than 10 years)
• Bone growth or fusion simulator
• Presence of cochlear, otologic or ear implant

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (2)

• 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.

  PMID: 23722696 BACKGROUND

• 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.

  PMID: 23985278 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Magnetic Resonance Spectroscopy

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

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Jennifer Goralski, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Participants undergoing treatment for a pulmonary exacerbation will perform multiple breath washout and undergo an MRI with inhalation of a gas contrast agent (79% perfluoropropane (PFP) mixed with 21% oxygen) at the beginning and end of treatment.

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 13, 2018
• Study Start: August 25, 2015
• Primary Completion: September 13, 2019
• Study Completion: September 13, 2019
• Last Updated: October 9, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)