NCT05924555

Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 50 (estimated)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

In this study, the exercise tolerance in patients with long-chain fatty acid oxidation disorders (LcFAOD) will be compared to that of healthy volunteers who are carefully matched in terms of age, sex, BMI and physical activity score. The study aims to assess exercise capacity using cardiopulmonary exercise (CPX) tests and activity monitoring over a 7-day period. The hypothesis of the study is that LcFAOD patients will exhibit greater oxygen debt during short periods of exercise compared to healthy individuals. These findings will contribute to a better understanding of exercise intolerance in LcFAOD patients and may guide the development of targeted interventions, such as exercise training programs and enable the analysis of effectiveness of (new) treatments.

Detailed description

Background:Long-chain fatty acid oxidation disorders (LcFAOD) are a group of autosomal recessive disorders that impair the utilization of long-chain fatty acids as an energy source. Exercise intolerance is a commonly reported symptom in adult patients with LcFAOD, but its severity varies significantly among individuals. In addition, little is currently known about the natural progression of exercise intolerance in this group of patients, and reliable outcome measures to assess treatment efficacy remain scarce. In this study, we will evaluate the exercise capacity in LcFAOD patients using intermittent CPX, and determine whether this yields outcome parameters that can be used to determine the course of exercise intolerance over the patients lifetime and evaluate treatment effectiveness. Hypothesis: Exercise intolerance in LcFAOD patients will be reflected in differences in VO2/VCO2 and heart rate kinetics during short periods of exercise compared to healthy subjects. Primary Objective: 1. Objectify and quantify exercise intolerance in LcFAOD patients. 2. Determine the relationship between the measured exercise intolerance and patient-reported symptoms, daily life functioning, as well as known markers of disease severity. Secondary Objective(s): 3. Determine the aetiology of exercise intolerance in LcFAODs. 4. Determine whether the intermittent exercise protocol can be used to establish the course of exercise intolerance and provide clinical outcome measure for future intervention studies. Methods: Participants will be asked to wear an activity monitor (Activ8) for a period of 7 days. The participants will also perform two cardiopulmonary exercise (CPX) tests (one intermittent and one incremental). During the CPX tests gas exchange, ventilation, blood pressure and cardiac output will be measured and exhaustion level monitored. Blood samples will be taken before the first and after the second CPX test. The grip strength (Maximal Voluntary Contraction) and the leg muscle size (echography) will be assessed. Body composition (using BIA) will be assessed. Approximately a year later all procedures, including the wearing of the activity monitor, will be repeated in all patients. Some participants will be asked to perform the two exercise tests again within two weeks of their first visit. This way reproducibility of the intermittent exercise protocol can be tested.

Conditions

• Long-chain Fatty Acid Oxidation Disorders

Interventions

Type	Name	Description
OTHER	Intermittent cardiopulmonary exercise test	Exercise test with step-change from rest to a relatively low constant workload.
OTHER	Incremental cardiopulmonary exercise test	Exercise test with incremental workload until maximal workload.
OTHER	Echography of upper leg	Determine upper leg muscle size
OTHER	Hand grip strength with hand dynamometer	Determine muscle strength
OTHER	Fill in questionnaires regarding physical activity	SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.

Timeline

• Start date: 2023-08-01
• Primary completion: 2028-08-01
• Completion: 2028-08-01
• First posted: 2023-06-29
• Last updated: 2024-08-23

Locations

1 site across 1 country: Netherlands