Exercise in People With Cystic Fibrosis on CFTR Modulator Therapy (FIQMODE)

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.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Exercise

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margarita Pérez Ruiz, PhD; Phone Number: Ext. 77960 +34910677960; Email: margarita.perez@upm.es

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Facultad de Ciencias de la Actividad Física y Deporte - INEF UPM
    • Contact: Marcela González Gross, PhD; Phone Number: +34910677980; Email: marcela.gonzalez.gross@upm.es
    • Principal Investigator: Margarita M Pérez-Ruiz, PhD
    • Sub-Investigator: Marcela González-Gross, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Telematic 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.	Other: Exercise; 16-week exercise intervention: At the beginning of the intervention, we will conduct a face-to-face familiarisation session with the exercises of the training programme. The intervention will consist of 2 sessions/week for 16 weeks. Each session consists of three stages: (i) Warm-up: 10 min of joint mobility and low intensity exercises involving the musculature to be worked in that session; (ii) Main part: circuit training mainly composed of strength exercises targeting the different muscle groups of the body and playing activities (iii) Cool down: 10 min with guided breathing work and stretching of the main muscle groups worked
No Intervention: Control; Control group will follow routine recommendations from the multidisciplinary CF team based on WHO´s guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in peripheral muscle strength	Upper and lower limbs muscle strength (kg) will be evaluated using dynamometers.	Baseline, pre-intervention and immediately after the intervention.
Changes in inspiratory/expiratory muscle strength (MIP/MEP) (cmH2O)	Inspiratory and expiratory muscle strength: maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) will be measured.	Baseline, pre-intervention and immediately after the intervention
Changes in functional capacity: lower limbs power capacity	30 seconds sit-to-stand test. Unit of measurement: number of repetitions.	Baseline, pre-intervention and immediately after the intervention
Changes in functional capacity: walking capacity	10m Time (s) Up and Go tests.	Baseline, pre-intervention and immediately after the intervention
Change in Cardiorespiratory fitness: maximal oxygen consumption	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.	Baseline, pre-intervention and immediately after the intervention
Change in Cardiorespiratory fitness: Ventilatory threshold VT1	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).	Baseline, pre-intervention and immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pulmonary Function: forced vital capacity (FVC)	Spirometry will assess: forced vital capacity (FVC) in milliliters and percentage of predicted value	Baseline, pre-intervention and immediately after the intervention
Changes in Pulmonary Function: Forced expiratory volume in the first second (FEV1)	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.	Baseline, pre-intervention and immediately after the intervention
Changes in the anthropometric and body composition: Weight	Weight (kg)	Baseline, pre-intervention and immediately after the intervention
Changes in the anthropometric and body composition: Height	Height (cm)	Baseline, pre-intervention and immediately after the intervention
Changes in the anthropometric and body composition: BMI	BMI (kg/m2)	Baseline, pre-intervention and immediately after the intervention
Changes in body composition: Total fat mass	Total fat mass (kg)	Baseline, pre-intervention and immediately after the intervention
Changes in body composition: FMI	fat mass index (FMI) (kg/m2),	Baseline, pre-intervention and immediately after the intervention
Changes in body composition: lean mass kg	Lean mass in kg	Baseline, pre-intervention and immediately after the intervention
Changes in body composition: lean mass %	Lean mass in %	Baseline, pre-intervention and immediately after the intervention
Changes in quality of life using the Cystic Fibrosis Questionnaire	Scores range from 0 to 100 with higher scores corresponding to better quality of life.	Baseline, pre-intervention and immediately after the intervention
Changes in plasma levels muscle damage biomarkers	Blood levels biomarkers of muscle damage as CK measured in micrograms per litre (mcg/L)	Baseline, pre-intervention and immediately after the intervention
Changes in plasma levels of inflammation: hs-CRP	High-sensitivity C-reactive protein (hs-CRP) assay in milligrams/litre	Baseline, pre-intervention and immediately after the intervention
Changes in plasma levels of inflammation: Interleukins	Analysis of interleukins such as IL6, IL-10 in picograms/millilitre	Baseline, pre-intervention and immediately after the intervention

Collaborators and Investigators

• Sponsor: Universidad Politecnica de Madrid
• Collaborators: Hospital Infantil Universitario Niño Jesús, Madrid, Spain; Hospital Universitario Ramon y Cajal; Carlos III Health Institute; Universidad Europea de Madrid; Hospital Universitario La Paz
• Investigators: Principal Investigator: Margarita Perez Ruiz, PhD, Universidad Politecnica de Madrid

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Estimated): December 23, 2025
• Study Completion (Estimated): December 23, 2025

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Muscle Strength; Resistance Training; Physical Fitness; Lung funcion
• 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: PI23/00299

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