Long-chain Fatty Acid Oxidation DisordersEXCITE LcFAODNCT05924555
Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders
An observational study of Long-chain Fatty Acid Oxidation Disorders, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Long-chain Fatty Acid Oxidation Disorders
- What is being tested?
- Intermittent cardiopulmonary exercise test, Incremental cardiopulmonary exercise test and Echography of upper leg
- How many people
- 50 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2023to 1 Aug 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: All adult patients with long chain fatty acid oxidation disorders are under follow-up are eligible to participate in the study. Each patients will be compared to a matched healthy control subject (one healthy subject can serve as a control for more than one LcFAOD patient). Matching will be done by age (± 3 years), sex, BMI (± 2 kg/m2) and a comparable activity score assessed using a questionnaire (the Short Questionnaire to Asses Health enhancing physical activity (SQUASH).
Who may be able to join
- 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
Who cannot join
- 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
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- 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:
- All abovementioned exclusion criteria for LcFOAD patients
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC, location AMC
Amsterdam, North Holland, 1105 AZ
About this study
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.
Read the 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.
- Being tested
- Intermittent cardiopulmonary exercise test, Incremental cardiopulmonary exercise test, Echography of upper leg, Hand grip strength with hand dynamometer, Fill in questionnaires regarding physical activity
- Keywords
- Long-chain Fatty Acid Oxidation disorders, Exercise intolerance, Cardiopulmonary exercise test
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent cardiopulmonary exercise testOther
Exercise test with step-change from rest to a relatively low constant workload.
Incremental cardiopulmonary exercise testOther
Exercise test with incremental workload until maximal workload.
Echography of upper legOther
Determine upper leg muscle size
Hand grip strength with hand dynamometerOther
Determine muscle strength
Fill in questionnaires regarding physical activityOther
SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.
| Study group | Role | What they receive |
|---|---|---|
| LcFAOD-patients | Patients with long-chain Fatty Acid Oxidation including CPT2-, CACT-, VLCAD-, LCHAD-, or MTP-deficiency Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test; Other: Echography of upper leg; Other: Hand grip strength with hand dynamometer; Other: Fill in questionnaires regarding physical activity | |
| Healthy controls | Controls are matched based on Age, Sex, BMI and comparable activity score assessed using the SQUASH questionnaire Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test; Other: Echography of upper leg; Other: Hand grip strength with hand dynamometer; Other: Fill in questionnaires regarding physical activity |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Differences in V'O2/ V'CO2/heart rate kinetics during the intermittent exercise test between LcFAOD patients and healthy control subjects
Measured: At rest (baseline) and during the intermittent CPX test (30 min)
Anaerobic threshold (ml/kg/min)
Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations
Measured: During maximum exercise (max 30 min).
Ventilation reserve (L)
Pulmonary involvement/Skeletal muscle alterations
Measured: During maximum exercise (max 30 min).
CO2 ventilation equivalent (L/L)
Pulmonary involvement/Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
Cardiac Output (L/min)
Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
Heart rate reserve (per minute)
Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
Muscle size on echography (cm)
Skeletal muscle alterations
Measured: Baseline
Muscle strength via resistance test (kg)
Skeletal muscle alterations
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start1 Aug 2023
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long-chain Fatty Acid Oxidation DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- Stichting Stofwisselkracht
- Responsible party
- Principal investigator, Dr. Mirjam Langeveld, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Mirjam Langeveld, MD PhD, Principal investigator, Amsterdam UMC, location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05924555
- Sponsor's protocol ID
- NL83869.018.23
- Acronym
- EXCITE LcFAOD
- Status last verified
- Aug 2024
- First submitted
- 21 Jun 2023
- Last updated
- 23 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders
- ClinicalTrials.gov ID
- NCT05924555
- Acronym / sponsor ID
- EXCITE LcFAOD / NL83869.018.23
- Keywords
- Long-chain Fatty Acid Oxidation disorders, Exercise intolerance, Cardiopulmonary exercise test
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Stichting Stofwisselkracht
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 29 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LcFAOD-patients | – | Other: Intermittent cardiopulmonary exercise test, Other: Incremental cardiopulmonary exercise test, Other: Echography of upper leg, Other: Hand grip strength with hand dynamometer, Other: Fill in questionnaires regarding physical activityPatients with long-chain Fatty Acid Oxidation including CPT2-, CACT-, VLCAD-, LCHAD-, or MTP-deficiency |
| Healthy controls | – | Other: Intermittent cardiopulmonary exercise test, Other: Incremental cardiopulmonary exercise test, Other: Echography of upper leg, Other: Hand grip strength with hand dynamometer, Other: Fill in questionnaires regarding physical activityControls are matched based on Age, Sex, BMI and comparable activity score assessed using the SQUASH questionnaire |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All adult patients with long chain fatty acid oxidation disorders are under follow-up are eligible to participate in the study. Each patients will be compared to a matched healthy control subject (one healthy subject can serve as a control for more than one LcFAOD patient). Matching will be done by age (± 3 years), sex, BMI (± 2 kg/m2) and a comparable activity score assessed using a questionnaire (the Short Questionnaire to Asses Health enhancing physical activity (SQUASH).
Key inclusion criteria (4 listed)
- 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 men and women age ≥ 18 years
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intermittent cardiopulmonary exercise testExercise test with step-change from rest to a relatively low constant workload. | Other | Healthy controls, LcFAOD-patients |
| Incremental cardiopulmonary exercise testExercise test with incremental workload until maximal workload. | Other | Healthy controls, LcFAOD-patients |
| Echography of upper legDetermine upper leg muscle size | Other | Healthy controls, LcFAOD-patients |
| Hand grip strength with hand dynamometerDetermine muscle strength | Other | Healthy controls, LcFAOD-patients |
| Fill in questionnaires regarding physical activitySQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients. | Other | Healthy controls, LcFAOD-patients |
Primary outcome
1. Differences in V'O2/ V'CO2/heart rate kinetics during the intermittent exercise test between LcFAOD patients and healthy control subjects
Time frame: At rest (baseline) and during the intermittent CPX test (30 min)
Anaerobic threshold (ml/kg/min)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations
Ventilation reserve (L)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Skeletal muscle alterations
CO2 ventilation equivalent (L/L)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Cardiac dysfunction
Cardiac Output (L/min)
Time frame: During maximum exercise (max 30 min).
Cardiac dysfunction
Heart rate reserve (per minute)
Time frame: During maximum exercise (max 30 min).
Cardiac dysfunction
Muscle size on echography (cm)
Time frame: Baseline
Skeletal muscle alterations
Muscle strength via resistance test (kg)
Time frame: Baseline
Skeletal muscle alterations
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mirjam Langeveld, MD PhD principal investigator
Amsterdam UMC, location AMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Long-chain Fatty Acid Oxidation Disorders, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Khya Snelder, BSc (20 5666791 ext. +31, c.k.snelder@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Differences in V'O2/ V'CO2/heart rate kinetics during the intermittent exercise test between LcFAOD patients and healthy control subjects (time frame: At rest (baseline) and during the intermittent CPX test (30 min)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.