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…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Differences in V*O2 kinetics during the intermittent exercise test between
LcFAOD patients and healthy control subjects (objective 1)
2. Differences in parameters reflecting pulmonary, cardiac and skeletal muscle
function during exercise between LcFAOD patients and healthy control subjects
(objective 3). The following parameters will be taken into account:
- Pulmonary function:
Pulmonary function test: FEV1/VC (Tiffeneau-index) at rest. During maximum CPX
test: V*O2 max, anaerobic threshold (AT), ventilation (VE) reserve, CO2
ventilation equivalent (EqCO2) and O2 saturation and O2 (pulse oximetry, SpO2).
- Cardiac function:
During maximum CPX: V*O2 max, HR reserve, Cardiac output (CO) and AT, EqCO2 and
a O2 pulse plateau. NT-proBNP and troponin in plasma.
- Skeletal muscle function:
During maximum CPX: V*O2 max, AT, VE reserve. Muscle size and strength
(resistance test and echography). CK, lactate, ammonia in plasma.
3. Associations of VO2 kinetics during the intermittent test with the VO2 max
in the incremental test, daily physical activity measured using the
accelerometer, the SQUASH score and the patient-reported myopathic symptoms
(objective 2).
4. Differences in measured (using an accelerometer) and reported (using
questionnaires) daily physical activity between lcFAOD patients and healthy
controls (objective 1).
5. Reproducibility of the VO2 kinetics during the intermittent test as well as
the changes in these parameters in response to an intervention
(training)(objective 4).
Secondary outcome
1. The body fat percentage in LcFAOD patients compared to that of healthy
controls.
Background summary
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 and evaluate treatment effectiveness.
Study objective
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 as clinical outcome measure in
future intervention studies.
Study design
A monocenter prospective cohort study.
Study burden and risks
1. The number of site visits: During this study, there will be 2 mandatory site
visits of 5 hours each. In case the participants is taking part in the optional
exercise test visit, there will be an extra site visit of 5 hours. Total hours
for site visits: 10 hours. In case of extra visit: 15 hours.
2. Questionnaires: three questionnaires SQUASH, modified medical research
council (mMRC) dyspnea scale, and a questionnaired designed to evaluate
myopathic symptoms in lcFAOD*s. The setimated time to fill in these three
questionnairs is 30 minutes.
3. Study procedures: Bioelectrical impedance analysis, strengh test, echography
of the upper leg, rest spirometry, maximum incremental and intermittent CPX
test. The estimated time for all these procedures is five hours. Participants
will have to undergo these procedures twice (the second time aproximately a
year later). Thus in total, participants will spend 10 hours of their time
undergoing these procedures during the study. If patient participate in the
optional exercise visit they will spend an extra 4-5 hours performing the
maximum incremental and intermittent CPX test. (All participants will also have
to wear an an activity monitor at home during 7 days.)
4. Blood and other tests: intravenous blood will be taken at four points. The
total blood voume that will be drawn is 60 ml. The risk of drawing blood may
include some dizziness, discomfort around the bruise and a very low risk of
infection.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
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 control subjects: - 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83869.018.23 |