Airway Clearance Therapy on Hyperpolarized 129Xenon and MRI

The Effect of Airway Clearance Therapy on Hyperpolarized 129Xenon MRI Compared With Lung Clearance Index and Spirometry in Cystic Fibrosis

This is an observational cohort study building on an existing protocol at our institution recruiting CF patients who are 6-21 years old with one or two copies of the F508del CFTR mutation. That existing protocol seeks to enroll a total of 38 subjects; it includes three to four (three scheduled, with a fourth optional) study visits, with spirometry, LCI, UTE MRI, and 129Xe MRI being performed at each visit. This present study will utilize existing study visits for the NHLBI study, with a sub-set of 20 subjects opting-in to have all of the procedures performed twice, with an intervening ACT, during one of their study visits.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: hyperpolarized Xenon gas

Detailed Description

This is an observational cohort study building on an existing protocol at our institution recruiting CF patients who are 6-21 years old with one or two copies of the F508del CFTR mutation. The existing protocol is funded by the NHLBI under R01-11863962 (PIs Woods, Clancy, and hereafter referred to as "the NHLBI study" for simplicity), and seeks to enroll a total of 38 subjects; it includes three to four (three scheduled, with a fourth optional) study visits, with spirometry, LCI, UTE MRI, and 129Xe MRI being performed at each visit. This present study will utilize existing study visits for the NHLBI study, with patients opting-in to have all of the procedures performed twice, with an intervening ACT, during one their study visits. The target enrollment is 20 subjects.

Airway clearance therapy (ACT) is used for treating cystic fibrosis (CF). It is known to impact measures of lung function, and while an increasing number of lung function measures are used in clinical trials, there has been no direct comparison of the effects of ACT across the different modalities. This study is actively investigating the relationship between different measures of lung function, comparing a spirometric measure (FEV1 percent-predicted) with measures of whole-lung ventilation (lung clearance index, or LCI) and regional assessments of both structure (with ultra-short echo time magnetic resonance imaging, or UTE MRI) and function (with hyperpolarized xenon, or 129Xe, MRI). Performing these assessments on CF patients will help to elucidate the relative sensitivity of each measure to intra-individual changes within the lung and will help guide the selection of lung function measures in future studies.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 42229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male or female ages 6 through 21 with CF

Description

Inclusion Criteria:

• Male or female between the ages of 6 through 21 years
• CFTR genotypes as specified in NHLBI study:

Two copies of the F508del CFTR mutation, OR Two non-functional CFTR mutations with one of them being F508del CFTR mutation

• Able to perform acceptable and repeatable spirometry

Exclusion Criteria:

• FEV1 percent predicted of <60%
• standard MRI exclusions (metal implants, claustrophobia)
• pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of ACT on 129Xe MRI	Quantify the effect of ACT on 129Xe MRI in ventilation defect percentage (%), in 20 children ages 6-21 years with CF	one-day single study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of ACT on spirometry	Quantify the effect of ACT on spirometry in indexed values of FEV1, in percentage (%), in 20 children ages 6-21 years with CF	one-day single study visit
Effect of ACT on LCI	Quantify the effect of ACT on lung clearance index (LCI) in LCI2.5 values, in 20 children ages 6-21 years with CF	one-day single study visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural changes on UTE MRI	Describe the structural changes on UTE MRI that occur with airway clearance and correlate these with changes in spirometry and measures of ventilation heterogeneity	one-day single study visit

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jason Woods, PhD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: ACT and Xe MRI; 1R01HL131012-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED