To investigate whether patients with VLCADD have a different energy metabolism compared to healthy controls.
ID
Source
Brief title
Condition
- Inborn errors of metabolism
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
o Blood parameters: glucose, lactaat, creatine kinase (CK)
o Resting, and FATMAX exercise phoscreatine (PCr)
o Resting, and FATMAX Inorganic phosphorus (Pi)
o Resting, and FATMAX pH
o Resting and FATMAX phosphate potential (delta GP)
o Resting, and FATMAX hexose monophosphates (HMP)
o Resting, and FATMAX IMCL content
o Stroke volume
o Urine: myoglobine
Secondary outcome
o Peak workload (Wpeak)
o Resting and peak oxygen uptake (VO2peak/kg (ml/min/kg) )
o Resting and peak minute ventilation (VEpeak) (L/min)
o Resting and peak respiratory exchange ratio (RER = VCO2/VO2)
o Resting and peak heart rate (HR; bpm)
Background summary
VLCADD is a rare disorder affecting the mitochondrial beta-oxidation of
long-chain fatty acids. Clinical symptoms such as hypoglycaemia and
(cardio)myopathy arise, or are exacerbated during catabolic situations e.g.
during illness or fasting. Age at onset, manifestation patterns and clinical
severity differ between patients. Dietary treatment -the only therapeutic
option- will prevent hypoglycaemic episodes, however it does not reduce
myopathy. One of the most prominent symptoms of patients with VLCADD is
myopathy induced by the breakdown of myocytes (rhabdomyolysis). Rhabdomyolysis
is provoked by fasting, fever, cold, medication, and exercise from infancy to
adulthood. The pathophysiology of these episodes of rhabdomyolysis is not
completely understood. The symptoms might be caused by 1) an energy shortage
due to the fatty acid oxidation (FAO) defect and/or 2) toxicity caused by the
accumulation of FAO intermediates, or 3) by meta-flammation: inflammation
caused by abnormal metabolites. Insight into the pathophysiology of muscle
metabolism in patients with VLCADD can be used to understand and (eventually)
treat myopathy that accompanies this disease.
Recently, 31 Posphate and 1 Proton magnetic resonance spectroscopy (31P/1H
MRS)has been shown to non-invasively assess muscle metabolism in-vivo during
rest, but also during exercise and recovery. In the proposed study, 31P MRS
and 1Proton MRS measurements will be combined with a cardiopulmonary exercise
test (CPET) on a cycle ergometer.
Study objective
To investigate whether patients with VLCADD have a different energy metabolism
compared to healthy controls.
Study design
A case-controlled study using a novel MRS technique.
Study burden and risks
In clinical practice, many parents wonder to which extent their children will
be able to perform exercise. The same applies to adults. This study will gain
insight into physical abilities and inabilities of children and adults with
VLCADD. This insight will be used to advice patients to what extent they can
participate in physical activities and at what intensity. In addition, more
rhabdomyolytic episodes have been observed in children with VLCADD opposed to
adult patients. As the metabolic response to exercise of children with VLCADD
might be different compared to adult patients, it is also important to perform
these exercise tests in patients between 12 and 18 years of age when studying
the muscle metabolism during rest, exercise and recovery (group relatedness).
Participation in the first test will take in total 45 minutes, including a 8-12
min maximal exercise test. To provide the shortest possible exercise duration,
step rates on the bicycle are individualised to yield test durations of
approximately 10 minutes for each volunteer. The second test will take 270 min,
including a 45 min submaximal (~30% of max.) exercise test and recovery time
after the test. Both tests will be performed during two separate test sessions
on two different days.
Since the maximum exercise test will use anaerobic derived energy and the
endurance test will be at a submaximal level (30% of max.), the burden for
controls is very small. No muscle pain is expected. As patients with VLCADD do
not have a problem with anaerobic glycolysis, the burden for the maximal
exercise test will also be very small. The endurance test at submaximal level
might induce muscle pain temporarily, becasue the aerobic system is affected in
VLCADD patients. We therefore classify the burden for patients as minimal and
will monitor these patients accordingly during the study period. Blood will be
drawn intravenously from patients between 12 and 45 years of age. This implies
a minimal burden. To minimize the burden for young controls, blood will only be
drawn from adult controls.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
Patients with VLCADD
- diagnosis confirmed by enzyme assay and mutation analysis
- between 12 and 45 years
Healthy controls:
- between 12 and 45 years
- free from constraints in performing a maximal exercise test
Exclusion criteria
Patients with VLCADD:
- ineligible to perform an exercise test
- pregnancy
- myopathic exacerbation at time of investigation
- with severe complications due to cardiomyopathy/arrythmia
- with severe complications due to epilepsia
- not familiar with the Dutch language
- presence of contra-indications for 31P/1H MRS measurements (assessed by standardised questionnaire as previously used in METC 08-267/K; see section F METC documents)
Healthy controls:
- ineligible to perform an exercise test (assessed by a standardised questionnaire as previously used in METC 10-468)
- not familiar with the Dutch language
- presence of contra-indications for 31P/1H MRS measurements (assessed by a standardised questionnaire as previously used in METC 08-267/K)
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 | NL38965.041.12 |