Assessment of CFTR-Modulator Treatment in Cystic Fibrosis Lung Disease Using Novel Structural and Functional MRI

In this study, MRI of the lungs of healthy volunteers and participants with cystic fibrosis (stable and participants initiating CFTR modulator treatment) will be performed over a period of 6 months to determine if lung MRI is able detect structural and functional abnormalities/changes in early cystic fibrosis disease. During the 6 month period, 3 study visits will occur. 70 subjects aged 6 and older will participate in this study. Xenon MRI is a non-invasive imaging technique that does not involve x-rays or ionizing radiation. Rather, this imaging method utilizes the same hardware and software principles that are used for conventional proton MRI of patients in a hospital.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Giles Santyr; Phone Number: 301394 4168137654; Email: giles.santyr@sickkids.ca
• Study Contact Backup: Name: Sharon Braganza; Phone Number: 307937 4168137654; Email: sharon.braganza@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • The Hospital for Sick Children
      • Principal Investigator: Giles Santyr, PhD FCCPM
      • Contact: Giles Santyr, PhD FCCPM; Email: giles.santyr@sickkids.ca
      • Contact: Sharon Braganza, M.Sc; Phone Number: 307937 416 813 7654; Email: sharon.braganza@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This study includes three populations of interest: Group 1: 25 healthy volunteers, Group 2: 25 patients with stable CF lung disease and Group 3: 20 patients with CF lung disease anticipated to receive treatment with CFTR-modulator therapy.

Description

Inclusion Criteria:

• Participants must be greater than or equal to 6 years of age
• Informed consent by patient or parent/guardian consent and participant assent when appropriate.
• Able to perform reproducible spirometry and achieve a breath hold duration sufficient for MRI acquisition

Exclusion Criteria:

• Medical instability that would preclude the ability to undergo the required investigations
• FEV1 % predicted < 40%
• Severe claustrophobia
• Does not meet MRI screening criteria
• Cough within the past 3 days prior to study visit
• Usage of oral antibiotics within 3 weeks prior to study visit

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; Healthy participants without lung disease
Group 2; Participants with stable cystic fibrosis
Group 3; Participants with cystic fibrosis, anticipated to receive treatment with CFTR-modulator therapy. Please note: treatment is determined by your physician as part of your normal therapy plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproducibility	Establish the interscan reproducibility of MRI over three visits in healthy volunteers and in patients with stable CF lung disease and compare to conventional breathing tests	12 months
Responsiveness	Assess responsiveness of MRI to treatment effects over three visits in CF patients receiving CFTR-modulator therapy and compare to conventional breathing tests	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation	Correlate changes in lung structure and function detected by MRI imaging with clinical outcomes including FEV1 rate of decline, frequency of pulmonary exacerbations, days of IV antibiotics and hospital days to treat pulmonary exacerbation and change in health-related quality of life measures (CFQ-R scores and CF-QUEST) in the setting of patients with stable CF lung disease and those receiving CFTR-modulator therapy.	12 months

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Giles Santyr, PhD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Lung; CFTR modulator treatment; xenon MRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 1000063021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be shared between the two participating sites in the study. A data transfer agreement has been implemented to enable this transfer smoothly.
• IPD Sharing Time Frame: The data will be available after enrolling the first participant and will be available for the duration of the study
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No