Exercise Training Effects on Muscle Function in Adults With Mitochondrial Myopathy

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Copenhagen

About this trial

The goal of this observational study is to learn how exercise training affects molecular processes in skeletal muscle in adults with mitochondrial myopathy, compared with healthy adults.

The main questions it aims to answer are:

* How does exercise training affect mitochondrial activity and energy production pathways in skeletal muscle in people with mitochondrial myopathy? * How does exercise training affect molecular signals related to muscle growth, stress responses, and muscle-nerve communication in people with mitochondrial myopathy?

Researchers will compare the trained leg to the untrained leg within the same participant, and also compare responses between participants with mitochondrial myopathy and healthy control participants, to see how molecular responses to exercise differ between groups.

The participants will:

* Complete a 3-4-week supervised exercise training program using one leg. * Undergo muscle biopsies from both the trained and untrained leg. * Complete basic muscle strength and physical function tests.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Known mtDNA or nuclear (nDNA) mutations

Age above or equal to 18 years

Disqualifiers

Medical conditions which deem the MM patient unfit to complete the study

Current use of medications known to interact with outcome measures. (see below)

Pregnancy

The participant is for any other reason unlikely to complete the study

Trial design

Design model

Parallel

Treatments tested in this trial

  • Unilateral high-intensity interval training (HIIT)

    Behavioral

    Participants will undergo ten sessions of HIIT of the leg randomized to the intervention while the inactive leg serves as the control leg

Treatment groups

22 Participants
are divided into 2 treatment groups
Group A: Mitochondrial MyopathyExperimental treatment 1 intervention
Group B: Healthy controlsActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Muscle mitochondrial respiration

Mitochondrial O2 flux is measured by high-resolution respirometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity

Time frame
24-72 hours after final training session
2

Muscle mitochondrial reactive oxygen species (ROS) production

Mitochondrial H2O2 emission rates are measured by high-resolution fluorometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity

Time frame
24-72 hours after final training session

Secondary outcomes

1

Muscle strength and endurance

Measured by an incremental one-legged test.

Time frame
At first, fifth and tenth training session
2

Muscle structure and neuromuscular junction morphology

Measured by histology and TEM from muscle biopsy specimens taken from both trained and untrained leg

Time frame
24-72 hours after final training session
3

Muscle integrated stress responses, growth and metabolic signaling

Measured by immunoblotting and Real-Time PCR in muscle biopsies from trained and untrained leg

Time frame
24-72 hours after final training session
4

Body and leg composition

as measured by whole-body DXA scanning

Time frame
Baseline and 24-72 hours after final training session

Other outcomes

1

Global unbiased exploratory metabolomic, lipidomic, proteomic, and microRNA profiling

From trained and untrained muscle biopsy samples from individuals with MM and matched healthy control subjects

Time frame
24-72 hours after final training session

Sponsors and contacts

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University of Copenhagen

Lead sponsor

Rigshospitalet, Denmark

Collaborator