Muscle Function and Physical Activity in the Modern Era of Cystic Fibrosis (MUCOMUSCLE)

Comparison of Muscle Function and Physical Activity Levels Between People With Cystic Fibrosis and Healthy Individuals in the Modern Era of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) Modulators: A Case-Control Study

Cystic fibrosis (CF) is characterized by various extrapulmonary manifestations, including altered skeletal muscle function, with both quantitative (e.g. reduced muscle mass) and qualitative (e.g. impaired oxidative function) impairments that may have a negative impact on exercise tolerance and quality of life. These abnormalities have traditionally been related to disease (e.g. systemic inflammation) or behavioral factors (e.g. increased physical inactivity). However, most of the studies that observed these abnormalities and tried to shed light on the underlying factors were either small or conducted before the widespread of CFTR (Cystic fibrosis transmembrane conductance regulator) modulators that have profound impact on the trajectory of the disease. While several studies suggested that the major recent improvements in therapeutics, including highly effective CFTR modulators, may have positive effects on skeletal muscle function, either directly (e.g. improved mitochondrial function) or indirectly (e.g. reduction in physical inactivity), no studies to date have thoroughly investigated this issue in a representative sample of people with CF. The absence of recent data on muscle function and physical activity levels casts doubt on the relevance of recommendations on exercise training in this population that were published before the widespread use of highly effective CFTR modulators. This study aims to compare muscle function, measured according to the latest recommendations of the European Cystic Fibrosis Society (Saynor et al., 2023), and physical activity of children and adults with CF under CFTR modulators, compared to age- and sex-matched healthy individuals. We hypothesize that the strength, endurance, muscle power, and physical activity levels of individuals with cystic fibrosis, treated with CFTR modulators, remain reduced compared to healthy individuals.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Volumetric ultrasound of the quadriceps and fitting of an accelerometer

• Study Type: Observational
• Enrollment (Estimated): 112

Contacts and Locations

• Study Contact: Name: Laurent MD MELY; Phone Number: +33 04 94 38 17 52; Email: laurent.mely@chu-lyon.fr
• Study Contact Backup: Name: Antoine-Raphaël MD Bronstein; Phone Number: +33 0662839256; Email: antoine-raphael.bronstein@chu-lyon.fr

Study Locations

• France
  • Hyères, France, 83400
    • Recruiting
    • HCL - Hôpital Renée Sabran
    • Contact: Laurent MD MELY; Phone Number: +33 04 94 38 17 52; Email: laurent.mely@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The population of patients with cystic fibrosis is selected from the patient cohort at Renée Sabran Hospital, a specialized center for the monitoring and treatment of patients with cystic fibrosis. The healthy individuals will be recruited in the general population from University and Hospital staff (including their children).

Description

Inclusion Criteria:

• Criteria for inclusion of CF patients:

  • Diagnosis of cystic fibrosis
  • Treated with CFTR modulator therapy
  • Men and women (children or adults) aged 10 years or older
  • Affiliated with or entitled to social security coverage
  • For people ≥ 18 years old: participant expressing its oral non-opposition
  • For minor child (<18 years old): participant and its legal representative expressing their oral non-opposition

• Criteria for inclusion of healthy subjects:

  • Men and women (children or adults) aged 10 years or older
  • Affiliated with or entitled to social security coverage
  • For people ≥ 18 years old: participant expressing its oral non-opposition
  • For minor child (<18 years old): participant and its legal representative expressing their oral non-opposition

Exclusion Criteria:

• Exclusion criteria for CF patients:

  • Lack of a stable clinical condition (defined here as the presence of a pulmonary exacerbation and/or a significant change in treatments in the three weeks preceding inclusion in the study).
  • Medical contraindication to engage in moderate-intensity physical activity.
  • Knee joint pain incompatible with the measurement of quadriceps strength.
  • Pregnancy.

• Exclusion criteria for healthy subjects:

  • Known chronic respiratory, cardiovascular, metabolic, renal, or neuromuscular diseases.
  • Presence of benign illnesses and/or acute infections requiring a doctor's visit and occasional treatment in the three weeks preceding inclusion in the study.
  • Medical contraindication to engage in moderate-intensity physical activity.
  • Knee joint pain incompatible with the measurement of quadriceps strength.
  • Pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
People with Cystic fibrosis treated with CFTR modulators; Children (over 10 years old) and adults with cystic fibrosis, with a stable clinical condition and no contraindications to engaging in moderate-intensity physical activities (PA).	Other: Volumetric ultrasound of the quadriceps and fitting of an accelerometer; The research procedure will simply involve a volumetric ultrasound of the quadriceps and the fitting of an accelerometer (watch worn on the wrist) for one week (collection of usual physical activities).
Healthy individuals; Healthy children (over 10 years old) and adults without known diseases (chronic respiratory, cardiovascular, metabolic, renal, or neuromuscular diseases) that may affect their peripheral muscle strength.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of isometric quadriceps strength (expressed in Newton), performed at René Sabran Hospital (as part of routine clinical practice for people with CF)	The quadriceps strength will be measured on an isometric chair according to the last recommendations of the European Cystic Fibrosis Society (Saynor et al., 2023). Briefly, participants will perform at least three maximal voluntary contractions of the knee extensors, each lasting 4-6s, with a minimal recovery of 1-min between each attempt, with the aim to obtain three maximal quadriceps strength values varying less than 5% (that is usually obtained in less than 6 trials). The highest strength value among these three attempts will be kept for analysis.	Day 0

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Physical activity; Cystic fibrosis; CFTR modulators; Muscle function
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 69HCL23_1226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No