Exercise in People With Cystic Fibrosis on CFTR Modulator Therapy

Effects of a Strength Exercise Program on Muscular Health in People With CF Treated With Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Receptor (CFTR)

Recently, the treatment of Cystic Fibrosis (CF) incorporated new modulators/enhancers of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). It is thus increasingly important to study the side effects of these drugs, their extrapulmonary effects and possible interaction with other drugs and with exercise. For this purpose, a randomized controlled trial is proposed to determine the effects of a telematic exercise intervention on muscle health, in a group of 48 children and adolescents with CF treated with these new generation CFTR modulators. They will be randomly assigned to two groups (exercise and control group). The effect of the intervention will be analysed measuring the variables of muscle health, cardiorespiratory fitness, lung function, body composition, inflammatory biomarkers and miRNAs. After completion of the intervention program, adherence to exercise and clinical evolution after one year will be analysed.

Specific objectives

1. To determine the effects of a strength exercise intervention in a group of children and adolescents with cystic fibrosis treated with new generation CFTR modulators on: (1.i) peripheral muscle strength; (1.ii) respiratory muscle strength; (1.iii) muscle mass and (1.iv) biomarkers of muscle damage.
2. To determine the effects of a strength exercise intervention in a group of children and adolescents with cystic fibrosis being treated with new generation CFTR modulators on: (2.i) cardiorespiratory fitness; (2.ii) body composition and (2.iii) lung function.
3. To determine the effects of a strength-based exercise intervention in a group of children and adolescents with cystic fibrosis treated with new-generation CFTR modulators on: (3.i) biomarkers of inflammatory status and (3.ii) expression of associated miRNAs.
4. To determine the effects of a strength-based exercise intervention in a group of children and adolescents with cystic fibrosis treated with the new generation CFTR modulators on the levels of Elexaxcaftor/Ivacaftor/Tezacaftor and their metabolites.
5. To assess the clinical evolution and adherence to exercise after 6 months of the programme in children and adolescents with cystic fibrosis treated with the new generation of CFTR modulators.

Inclusion Criteria:

• patients diagnosed with CF.
• patients between 6-20 years of age.
• patients receiving treatment with new CFTR protein modulating medication
• reading, acceptance and signing of the informed consent form.

Exclusion Criteria:

• CF patients with symptoms of pulmonary exacerbation during the last four weeks.
• with a diagnosis of other cardiorespiratory lung diseases progressing to a symptom of persistent respiratory dysfunction.
• CF patients with musculoskeletal alterations that influence assessments.
• CF patient who is pregnant during the time of the study
• CF patient with cognitive impairment;
• CF patient with incomplete dosing of modulator therapy;