Functional Muscle Characteristics and Cardio-respiratory Interaction in Patients With Fontan Palliation (FONTANEX)

Congenital heart disease (CHD) is the most common congenital defect, affecting about 1% of newborns. Among adults surviving complex CHD, the cohort of survivors after the Fontan palliation for univentricular physiology is the most rapidly growing. Given their unique physiology without a pumping chamber supporting the pulmonary circulation, their exercise capacity as adults is often severely reduced. Therefore, patients with grown-up CHD typically need long-term expert medical care causing constantly increasing healthcare- related costs. Specific exercise regimes might offer a safe, efficacious and cost-effective alternative to pharmacologic interventions and surgery. The underlying mechanisms of impaired exercise capacity in Fontan patients are, however, not fully understood and consequently, training regimes specifically tackling the limiting factors cannot be developed. In patients with CHD, studies have suggested that exercise limitations are secondary to the cardiac defects, factors related to cardiac surgery, chronotropic incompetence and underlying lung disease. Similar to heart failure patients, exercise limitations could be traced back to insufficient respiratory and leg muscle functions and impaired cardiovascular regeneration processes possibly due to an altered stem cell number and function in the peripheral blood.

The present study will investigate cardiac, respiratory and quadriceps muscle function at rest and during submaximal and maximal whole-body exercises. A special focus will be given on respiratory and quadriceps muscle strength, and proneness of these muscles to fatigue, which has not yet been objectively investigated. Moreover, different respiratory muscle training (RMT) protocols will be executed, to assess the safety of these interventions. Moreover, the current study will be the first to investigate the influence of exhaustive exercise protocols on the number and function of circulating stem and progenitor cells (CPCs) in Fontan patients. The number of these cell populations was shown to strongly correlate with long-term outcome and recovery in several diseases. This study aims to reveal whether Fontan patients show similarly alternated stem cell number and function in the peripheral blood, that likely result in impaired vascular regeneration processes and possibly also contribute to reduced exercise capacity.

Study Overview

• Status: Completed
• Conditions: Patients
• Intervention / Treatment: Other: Incremental cycling test (ICT); Other: Constant load cycling test (CET); Other: Incremental respiratory muscle test (IncRMET); Other: Incremental quadriceps muscle test (IncQMT); Other: Respiratory muscle training like interventions

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zürich, ZH, Switzerland, 8057
      • Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18 - 55 years
• Fontan palliation (for Fontan patients)
• NYHA I - III (for Fontan patients)
• Willing to adhere to the study rules

Exclusion Criteria:

• NYHA IV (for Fontan patients)
• not being able to perform cycle exercise
• known diaphragmatic paresis
• being pregnant or breast feeding
• Intention to become pregnant during the course of the study
• known or suspected non-compliance, drug or alcohol abuse
• Regular intake of medication affecting sleep or the performance of the respiratory, cardiovascular or neuromuscular system (except for Fontan-related medication for patients)
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
• previous enrolment in current study
• being investigator or his/her family member, employee or another dependent person

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient group; Incremental cycling test to volitional exhaustion. Constant load cycling test to volitional exhaustion. Respiratory and leg muscle endurance test to volitional exhaustion. Three respiratory muscle training interventions.	Other: Incremental cycling test (ICT); Incremental cycling test to volitional exhaustion; Other: Constant load cycling test (CET); Constant load cycling test to volitional exhaustion.; Other: Incremental respiratory muscle test (IncRMET); Incremental respiratory muscle test to volitional exhaustion.; Other: Incremental quadriceps muscle test (IncQMT); Incremental quadriceps muscle test to volitional exhaustion.; Other: Respiratory muscle training like interventions; Three different respiratory muscle training like interventions that are usually used for respiratory muscle trainings.
Active Comparator: Control group; The control group executes the same tests as the patient group.	Other: Incremental cycling test (ICT); Incremental cycling test to volitional exhaustion; Other: Constant load cycling test (CET); Constant load cycling test to volitional exhaustion.; Other: Incremental respiratory muscle test (IncRMET); Incremental respiratory muscle test to volitional exhaustion.; Other: Incremental quadriceps muscle test (IncQMT); Incremental quadriceps muscle test to volitional exhaustion.; Other: Respiratory muscle training like interventions; Three different respiratory muscle training like interventions that are usually used for respiratory muscle trainings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in respiratory muscle strength (in cmH2O)	Change in respiratory muscle strength will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)
Change in quadriceps muscle strength (in Newton)	Change in quadriceps muscle strength will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ventilation (in liter per minute)	Change in ventilation will be measured between baseline and after an acute exercise	On visit 1at baseline and after acute exercise (approximately 15 minutes)
Change in gas exchange (in liter per minute)	Change in gas exchange will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)
Change in heart rate (beats per minute)	Change in heart rate will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)
Change in cardiac output (in liter per minute)	Change in cardiac output will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)
Change in blood pressure (in mmHg)	Change in cardiac output will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)
Change in blood oxygen saturation (in %)	Change in blood oxygen saturation will be measured between baseline and after an acute exercise	At baseline and after acute exercise (approximately 15 minutes)

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: FONTANEX_2019

Drug and device information, study documents

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