To assess the effect of unilateral high intensity exercise training on in vivo protein synthesis rates of vastus lateralis muscle in patients with mitochondrial myopathy.
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study parameters include mitochondrial and myofibrillar protein
synthesis rates of vastus lateralis muscle, calculated from the increase in
enriched deuterized alanine in muscle tissue. The trained muscle will be
compared with the untrained muscle after 14 days of aerobic exercise.
Secondary outcome
Secondary study parameters are muscle tissue amino acid composition and
nitrogen content. Also mitochondrial respiration of muscle tissue from the
trained and untrained leg will be compared to baseline tissue using the
Oroboros technique.
Background summary
Mitochondrial myopathies are caused by genetic defects in proteins essential
for electron transfer chain function. The metabolic consequences of
mitochondrial dysfunction results from a decrease in aerobic energy production
from fat and carbohydrate oxidation, and tissues with high metabolic demand,
such as heart, brain, and skeletal muscle are particularly sensitive. Exercise
intolerance is a prominent symptom in patients with mitochondrial myopathy.
Aerobic training increases mitochondrial volume density and expression of
mitochondrial enzymes that facilitate aerobic metabolism. This will improve the
capacity to oxidize fat and thereby save limited carbohydrate stores from
becoming depleted. Effects on mitochondrial and myofibrillar protein syntheses
after an exercise intervention couldbe different in mitochondrial myopathies.
Study objective
To assess the effect of unilateral high intensity exercise training on in vivo
protein synthesis rates of vastus lateralis muscle in patients with
mitochondrial myopathy.
Study design
Non-randomized, pre-post unilateral intervention study with intra-individual
comparison.
Intervention
During a unilateral intervention period of 14 days, participants will perform
high intensity dynamic knee extension training with one leg every other day (in
total seven sessions). Based on leg dominance, the leg to be trained will
randomly be assigned.
Training session consist of 5 minutes warming-up, three sets of 4-min high
intensity training, separated by a 4-min break at very low intensity. Muscle
tissue protein synthesis rates will be assessed by ingesting deuterated water
(2H2O) throughout the interventional period. At baseline a muscle biopsy from
the vastus lateralis muscle will be performed in the control leg. After the
exercise intervention a muscle biopsy will be taken in both legs.
Study burden and risks
The risks involved in participating in this study are minimal. The muscle
biopsy will be obtained by a physician using the Bergström percutaneous needle
biopsy method. By using the unilateral training protocol, power will greatly
increase, the number of participants needed is reduced and the time needed to
perform this study is shortened in comparison with a cross-over or a
parallel-group design. Ingestion of deuterated water is safe and no adverse
side effects are associated with the ranges of the present study. Saliva
sampling for, determining body water 2H2O enrichment, is risk-free and blood
sampling is minimal (30mL total).
Reinier Postlaan 4
Nijmegen 6500 HB
NL
Reinier Postlaan 4
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Age >= 18 years
- m.3243A>G point mutation or single, large scale mtDNA deletion
Exclusion criteria
* insufficient mastery of the Dutch language
* pregnancy
* severe cardiopulmonary disease (chest pain, heart failure, arrhythmia,
pacemaker, cardiac surgery, severe exertional dyspnea, emphysema). If cardiac
involvement is present, inclusion will be evaluated by one of the cardiologists
with expertise in mitochondrial cardiomyopathy.
* coagulopathy (anti-platelet therapy is allowed)
* cognitive dysfunction
* not able to perform the high intensity training protocol
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 | NL81717.091.22 |