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Exercise in People With Cystic Fibrosis on CFTR Modulator Therapy

Not Applicable
Recruiting
Conditions
Cystic Fibrosis
Interventions
Other: Exercise
Registration Number
NCT06322446
Lead Sponsor
Universidad Politecnica de Madrid
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
48
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;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventionExerciseTelematic Exercise: A remotely supervised resistance exercise program will be carried out for 16 weeks, with two weekly sessions lasting approximately 60 minutes each. Training will be performed in groups of four patients, according to their lung function/physical fitness. The first training session will be on site (University) for familiarization, planning and adjustment of the exercises, and the following sessions will be performed online. Each session is divided into: (i) Warm-up and joint mobility; (ii) main part: strength exercises for different muscle groups; and (iii) cool down: stretching and breathing exercises.
Primary Outcome Measures
NameTimeMethod
Changes in peripheral muscle strengthBaseline, pre-intervention and immediately after the intervention.

Upper and lower limbs muscle strength (kg) will be evaluated using dynamometers.

Changes in inspiratory/expiratory muscle strength (MIP/MEP) (cmH2O)Baseline, pre-intervention and immediately after the intervention

Inspiratory and expiratory muscle strength: maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) will be measured.

Changes in functional capacity: lower limbs power capacityBaseline, pre-intervention and immediately after the intervention

30 seconds sit-to-stand test. Unit of measurement: number of repetitions.

Changes in functional capacity: walking capacityBaseline, pre-intervention and immediately after the intervention

10m Time (s) Up and Go tests.

Change in Cardiorespiratory fitness: maximal oxygen consumptionBaseline, pre-intervention and immediately after the intervention

To assess cardiorespiratory fitness, a treadmill and a gas analyser will be used. The test aims to determine maximal oxygen consumption (VO2peak in ml/kg/min). VO2peak will be recorded as the highest value obtained during a continuous 30 s period.

Change in Cardiorespiratory fitness: Ventilatory threshold VT1Baseline, pre-intervention and immediately after the intervention

To assess cardiorespiratory fitness, a treadmill and a gas analyser will be used. The test aims to determine the ventilatory threshold VT1 in response to maximal effort. VT1 will be determined using the criteria of an increase in both ventilatory equivalent for oxygen consumption (VE/VO2) and end-tidal oxygen pressure without an increase in ventilatory equivalent for carbon dioxide production (VE/VCO2).

Secondary Outcome Measures
NameTimeMethod
Changes in Pulmonary Function: forced vital capacity (FVC)Baseline, pre-intervention and immediately after the intervention

Spirometry will assess: forced vital capacity (FVC) in milliliters and percentage of predicted value

Changes in plasma levels of inflammation: hs-CRPBaseline, pre-intervention and immediately after the intervention

High-sensitivity C-reactive protein (hs-CRP) assay in milligrams/litre

Changes in Pulmonary Function: Forced expiratory volume in the first second (FEV1)Baseline, pre-intervention and immediately after the intervention

Spirometry will assess: forced expiratory volume in the first second (FEV1).Data will be expressed in absolute values and z-score based on the Global Lung Initiative (GLI) reference equation establishing as a limit of normality (LIN) a z-score value for FEV1 between -1.64 and + 1.64.

Changes in the anthropometric and body composition: HeightBaseline, pre-intervention and immediately after the intervention

Height (cm)

Changes in the anthropometric and body composition: BMIBaseline, pre-intervention and immediately after the intervention

BMI (kg/m2)

Changes in body composition: Total fat massBaseline, pre-intervention and immediately after the intervention

Total fat mass (kg)

Changes in body composition: lean mass kgBaseline, pre-intervention and immediately after the intervention

Lean mass in kg

Changes in body composition: lean mass %Baseline, pre-intervention and immediately after the intervention

Lean mass in %

Changes in quality of life using the Cystic Fibrosis QuestionnaireBaseline, pre-intervention and immediately after the intervention

Scores range from 0 to 100 with higher scores corresponding to better quality of life.

Changes in the anthropometric and body composition: WeightBaseline, pre-intervention and immediately after the intervention

Weight (kg)

Changes in body composition: FMIBaseline, pre-intervention and immediately after the intervention

fat mass index (FMI) (kg/m2),

Changes in plasma levels muscle damage biomarkersBaseline, pre-intervention and immediately after the intervention

Blood levels biomarkers of muscle damage as CK measured in micrograms per litre (mcg/L)

Changes in plasma levels of inflammation: InterleukinsBaseline, pre-intervention and immediately after the intervention

Analysis of interleukins such as IL6, IL-10 in picograms/millilitre

Trial Locations

Locations (1)

Facultad de Ciencias de la Actividad Física y Deporte - INEF UPM

🇪🇸

Madrid, Spain

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