Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders

NCT ID: NCT05924555

Last Updated: 2024-08-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-01

Study Completion Date

2028-08-01

Brief Summary

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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

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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

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Long-chain Fatty Acid Oxidation Disorders

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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LcFAOD-patients

Patients with long-chain Fatty Acid Oxidation including CPT2-, CACT-, VLCAD-, LCHAD-, or MTP-deficiency

Intermittent cardiopulmonary exercise test

Intervention Type OTHER

Exercise test with step-change from rest to a relatively low constant workload.

Incremental cardiopulmonary exercise test

Intervention Type OTHER

Exercise test with incremental workload until maximal workload.

Echography of upper leg

Intervention Type OTHER

Determine upper leg muscle size

Hand grip strength with hand dynamometer

Intervention Type OTHER

Determine muscle strength

Fill in questionnaires regarding physical activity

Intervention Type OTHER

SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.

Healthy controls

Controls are matched based on Age, Sex, BMI and comparable activity score assessed using the SQUASH questionnaire

Intermittent cardiopulmonary exercise test

Intervention Type OTHER

Exercise test with step-change from rest to a relatively low constant workload.

Incremental cardiopulmonary exercise test

Intervention Type OTHER

Exercise test with incremental workload until maximal workload.

Echography of upper leg

Intervention Type OTHER

Determine upper leg muscle size

Hand grip strength with hand dynamometer

Intervention Type OTHER

Determine muscle strength

Fill in questionnaires regarding physical activity

Intervention Type OTHER

SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.

Interventions

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Intermittent cardiopulmonary exercise test

Exercise test with step-change from rest to a relatively low constant workload.

Intervention Type OTHER

Incremental cardiopulmonary exercise test

Exercise test with incremental workload until maximal workload.

Intervention Type OTHER

Echography of upper leg

Determine upper leg muscle size

Intervention Type OTHER

Hand grip strength with hand dynamometer

Determine muscle strength

Intervention Type OTHER

Fill in questionnaires regarding physical activity

SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* LC-FAOD patients:
* Men and women (age ≥18 years) with a confirmed diagnosis of carnitine palmitoyltransferase 2 (CPT2) deficiency, Carnitine-acylcarnitine translocase (CACT) deficiency, Mitochondrial Trifunctional protein (MTP) deficiency, Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency or Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Healthy control subjects:

\- Healthy men and women age ≥ 18 years

Exclusion Criteria

LcFAOD patients:

* Pregnancy
* Recent acute myocardial infarction (\<6 months prior to inclusion)
* Uncontrolled arrhythmia/severe conduction disorder causing hemodynamic compromise
* Implantable pacemaker or other cardiac device with complete ventricular pacing
* Uncontrolled heart failure with hemodynamic compromise
* Uncontrolled hypertension (Systolic Blood Pressure \>150 mmHg and Diastolic Blood Pressure \>100 mmHg on repeated measurements)
* Active infection, anemia, severe renal dysfunction (estimated Glomerular filtration rate \< 30 ml/min/1,73m2), or other chronic disease likely to significantly impact exercise performance
* History of severe asthma or chronic obstructive pulmonary disease
* Active use of medication likely to affect exercise tolerance

Healthy controls:

* History of smoking - History of asthma, chronic obstructive pulmonary disease, heart failure, heart surgery, heart rhythm disorders or congenital heart diseases
* Chronic illness (including orthopedic, endocrinological, hematological, malignant, gastrointestinal, neurological, muscle or inflammatory disorders) likely to significantly impact on exercise performance
* \> 6 alcohol units per day or \> 14 alcohol units per week
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Stichting Stofwisselkracht

UNKNOWN

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Responsible Party

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Dr. Mirjam Langeveld

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mirjam Langeveld, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location AMC

Locations

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Amsterdam UMC, location AMC

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Khya Snelder, BSc

Role: CONTACT

20 5666791 ext. +31

Other Identifiers

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NL83869.018.23

Identifier Type: -

Identifier Source: org_study_id

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