Justification: Advances in therapies and patient care have led to dramatic improvements
in CF survival. Consequently, CF patients are living longer with varying degrees of lung
function impairment. Dyspnea is a commonly reported symptom in CF that adversely impacts
quality of life. Recently, elexacaftor/tezacaftor/ivacaftor (Trikafta), a combination
drug therapy, was approved by Health Canada for use in CF patients. Exercise capacity is
an important outcome parameter in CF and is a strong predictor of disease prognosis
including survival. Although previous research in patients on
elexacaftor/tezacaftor/ivacaftor combination therapy reported improved respiratory
symptoms and lung function, it remains uncertain as to whether this translates into
improvements in exercise performance. Stressing the respiratory system to its physiologic
limits through exercise might provide a more sensitive outcome measure to evaluate the
response to cystic fibrosis transmembrane regulator (CFTR) modulator therapy. Studies on
another CFTR modulator therapy combining lumacaftor and ivacaftor, have shown
inconclusive results on exercise tolerance in patients with CF when evaluated using an
incremental work rate exercise test protocol. However, a far more clinically and
physiologically relevant protocol in evaluating treatment effects is to use constant work
rate exercise tests and to evaluate dyspnea at standardized submaximal exercise times.
Additionally, changes in body composition shown to result from CFTR modulator therapy may
also have contributed to these inconclusive findings; however, body composition has not
been evaluated in previous CFTR studies.
Purpose: The purpose of this study is to determine the various factors that cause
shortness of breath (or dyspnea) in patients with cystic fibrosis (CF) and to determine
how treatment with Trikafta can manipulate these factors to improve shortness of breath
and exercise capacity.
Hypothesis: The investigators hypothesize that Trikafta will reduce dyspnea intensity
ratings and improve exercise capacity. These improvements will be associated with
improvements in the ventilatory response to exercise.
Objectives: To perform detailed cardiopulmonary exercise testing before and after the
initiation of Trikafta to evaluate its effect on exertional dyspnea and exercise
capacity, and to evaluate potential physiological mechanisms of improvement and the
impacts of changes in body composition.
Research Design: Observational study conducted over 4 visits. Participants with CF will
report to the Cardiopulmonary Exercise Physiology (CPEP) Laboratory on four separate
occasions. Visit 1 and 2 will occur before the participants go on drug (Trikafta) and
will be separated by a minimum of 48 hours between visits. Visit 3 and 4 will occur at 12
months and 24 months after initiating drug, respectively. On visit 1, participants will
complete medical history screening, anthropometric measurements, and a symptom limited
incremental cycle exercise test to determine peak incremental work rate. On visit 2,
participants will undergo a dual-energy X-ray absorptiometry (DEXA) scan, chronic
activity-related dyspnea questionnaires, quality of life questionnaires, physical
activity questionnaires, pulmonary function testing, and a constant-load cycle exercise
test at 80% of peak incremental work rate. Visits 3 and 4 will include chronic
activity-related dyspnea questionnaires, quality of life questionnaires, physical
activity questionnaires, a DEXA scan, pulmonary function testing, and a constant-load
cycle exercise test at 80% of peak incremental work rate. Data from the constant-load
cycle exercise tests performed on visits 2, 3, and 4 will address our hypothesis.