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

N/AActive Not RecruitingNCT04391322

The Hospital for Sick Children86 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

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

Eligibility

Sex: ALLMin age: 4 YearsMax age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 36 months

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.

Time frame: 12 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

Time frame: 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.

Time frame: 24 months