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

This is a prospective, longitudinal observational study conducted at The Hospital for Sick Children (SickKids). The purpose of this study is to evaluate the ability of MRI to detect changes in lung structure and function in CF patients receiving CFTR-modulator therapy. Participants who meet eligibility criteria and consent to the study will undergo study procedures which include spirometry and body plethysmography (optional), multiple breath washout testing, MRI and measurement of quality of life. The study will consist of three to six study visits for Group 1, 2 and 3: baseline, one month (±1 week) and 6 month (±2 week) and if they re-consent then 3 additional visits of 1 year (±6 months). (2 years (±6 months) and 3 years (±6 months) follow-up. Some participants in Group 2 may transition to Group 3.

This study includes three populations of interest: Group 1: 25 healthy volunteers, Group 2: 25 patients with stable CF lung disease , Group 3: 20 patients with CF lung disease anticipated to receive treatment with CFTR-modulator therapy and Group 4: 18 patients with CF who are between 4-8 years old and are starting triple combination modulator therapy using the rapid lung and abdominal imaging methods.

Study Overview

• Status: Active, not recruiting
• Conditions: Group 1: Healthy Controls; Group 2: Stable CF; Group 3: CF Participants Anticipated to Receive CFTR-modulator Therapy; Group 4: 4-8 yo CF Participants Starting Triple Combination Modulator Therapy

• Study Type: Observational
• Enrollment (Estimated): 86

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 100 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This study includes four 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 and Group 4: 18 patients with CF who are between 4-8 years old and are starting triple combination modulator therapy using the rapid lung and abdominal imaging methods

Description

Inclusion Criteria:

• Participants must be greater than or equal to 4 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

4

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.
Group 4; Participants with CF who are between 4-8 years old and are starting triple combination modulator therapy using the rapid lung and abdominal imaging methods.

What is the study measuring?

Primary 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
Reproducibility	Establish the interscan reproducibility of fractional ventilation maps and 1H MRI over three and up to six visits in healthy volunteers and in patients with stable CF lung disease and compare to conventional spirometry and LCI.	36 months
Responsiveness	Assess responsiveness of MRI to treatment effects over three and up to six visits visits in CF patients receiving CFTR-modulator therapy and compare to conventional breathing tests	36 months
Younger cohort	Extension of above objectives originally only explored in children ages 8-18 years old, to younger cohort of CF participants ages 4-8 years old at baseline prior to initiation of CFTR modulator therapy, as well as at 12 and 24 months after therapy initiation.	24 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 (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

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 (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Lung; CFTR modulator treatment; xenon MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Lung Diseases, Interstitial; 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; SAP; ICF; 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