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

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

• Registration Number: NCT04391322
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-18
• Study Start: 2020-10-20
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-12
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 86

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Reproducibility	36 months	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.
Correlation	12 months	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.
Responsiveness	36 months	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
Younger cohort	24 months	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.

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada