Mitochondrial DiseasesMM-EXNCT07450690
Exercise Training Effects on Muscle Function in Adults With Mitochondrial Myopathy
A study testing Unilateral high-intensity interval training (HIIT) in people with Mitochondrial Diseases and Mitochondrial Myopathy, run by University of Copenhagen at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases, Mitochondrial Myopathy
- What is being tested?
- Unilateral high-intensity interval training (HIIT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Jan 2026to 30 Oct 2030
- Phase
- Interventional
- 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
Who may be able to join
- Known mtDNA or nuclear (nDNA) mutations
- Age above or equal to 18 years
- Age above or equal to 18 years
Who cannot join
- 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
- Chronic medical conditions suspected to influence outcome measures
- Frequent use of medicine
- Pregnancy
- The participant is for any other reason unlikely to complete the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lykke Sylow, Ass.prof contact
Denmark1 site, 1 recruiting
- Recruiting
University of Copenhagen, Dept of Biomedical Sciences
Copenhagen, DK-2100
Lykke Sylow, Ass.prof, 0045 20955250, lykkesylow@sund.ku.dk
Johanne Modvig, M.Sc., johanne.modvig@sund.ku.dk
About this study
Official title: Deciphering Muscle-Nerve Communication Via Mitochondrial Myopathy Insights: Exploring the Effects of Exercise Training
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:
Read more
- 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.
Read the detailed description
Mitochondrial dysfunction is a central contributor to skeletal muscle weakness, metabolic dysregulation, and reduced physical capacity in mitochondrial myopathies. Defects in mitochondrial oxidative phosphorylation impair energy production and trigger maladaptive cellular stress responses, contributing to progressive muscle deterioration. While structured exercise training has been shown to improve mitochondrial oxidative capacity and functional performance in individuals with mitochondrial myopathy, the cellular and molecular pathways driving these adaptations are not fully defined.
This study employs a within-subject, parallel-group, unilateral exercise training model to examine exercise-induced adaptations in skeletal muscle from adults with mitochondrial myopathy and matched healthy controls. Participants undergo a 3-4-week supervised unilateral aerobic interval training program consisting of 10 sessions, with the trained leg randomized and the contralateral leg serving as an internal untrained control. This design increases statistical power and allows direct comparison of trained versus untrained muscle within the same individual.
Comprehensive phenotyping is conducted before the intervention, including assessments of muscle strength, functional performance, body composition, physical activity, and maximal oxygen uptake. Skeletal muscle biopsies obtained from both legs following the intervention enable detailed evaluation of mitochondrial respiratory function, mitochondrial morphology, neuromuscular junction structure, protein synthesis, signaling pathways, and unbiased multi-omics analyses (proteomics, phosphoproteomics, metabolomics, lipidomics, and transcriptomics).
By integrating physiological, molecular, and structural outcomes, this study seeks to elucidate mechanisms by which exercise training may partially reverse mitochondrial and neuromuscular defects in mitochondrial myopathy and establish exercise as a targeted therapeutic strategy for mitochondrial dysfunction.
- Conditions
- Mitochondrial Diseases, Mitochondrial Myopathy
- Being tested
- Unilateral high-intensity interval training (HIIT)
- Keywords
- Exercise training, Mitochondrial function, Skeletal Muscle, Neuromuscular Junction, Muscle Plasticity
- Medical subject headings
- Mitochondrial Diseases, Mitochondrial Myopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unilateral high-intensity interval training (HIIT)Behavioural
Participants will undergo ten sessions of HIIT of the leg randomized to the intervention while the inactive leg serves as the control leg
| Study group | Role | What they receive |
|---|---|---|
| Mitochondrial Myopathy | Experimental | Individuals with myopathy caused by mutations in nuclear or mitochondrial DNA Receives: Behavioral: Unilateral high-intensity interval training (HIIT) |
| Healthy controls | Active comparator | Control subjects matched for age, sex and BMI Receives: Behavioral: Unilateral high-intensity interval training (HIIT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24-72 hours after final training session
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
Measured: 24-72 hours after final training session
Secondary outcomes (4)
Muscle strength and endurance
Measured by an incremental one-legged test.
Measured: At first, fifth and tenth training session
Muscle structure and neuromuscular junction morphology
Measured by histology and TEM from muscle biopsy specimens taken from both trained and untrained leg
Measured: 24-72 hours after final training session
Muscle integrated stress responses, growth and metabolic signaling
Measured by immunoblotting and Real-Time PCR in muscle biopsies from trained and untrained leg
Measured: 24-72 hours after final training session
Body and leg composition
as measured by whole-body DXA scanning
Measured: Baseline and 24-72 hours after final training session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2026
- Study start9 Jan 2026
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial DiseasesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In a within-subject parallel-group longitudinal design, individuals with mitochondrial myopathy as well as matched controls sustain an exercise training intervention with one leg, while the contralateral leg serves as an inactive control.
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Lykke Sylow, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07450690
- Sponsor's protocol ID
- H-25048935
- Acronym
- MM-EX
- Status last verified
- Mar 2026
- First submitted
- 12 Jan 2026
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Saltin B, Nazar K, Costill DL, Stein E, Jansson E, Essen B, Gollnick D. The nature of the training response; peripheral and central adaptations of one-legged exercise. Acta Physiol Scand. 1976 Mar;96(3):289-305. doi: 10.1111/j.1748-1716.1976.tb10200.x.
PubMed 132082Porcelli, S., Grassi, B., Poole, D.C., Marzorati, M., 2019. Exercise intolerance in patients with mitochondrial myopathies: perfusive and diffusive limitations in the O2 pathway. Current Opinion in Physiology 10, 202-209. https://doi.org/10.1016/j.cophys.2019.05.011
Murphy JL, Blakely EL, Schaefer AM, He L, Wyrick P, Haller RG, Taylor RW, Turnbull DM, Taivassalo T. Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain. 2008 Nov;131(Pt 11):2832-40. doi: 10.1093/brain/awn252.
PubMed 18984605MacInnis MJ, Zacharewicz E, Martin BJ, Haikalis ME, Skelly LE, Tarnopolsky MA, Murphy RM, Gibala MJ. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. 2017 May 1;595(9):2955-2968. doi: 10.1113/JP272570. Epub 2016 Aug 3.
PubMed 27396440La Morgia C, Maresca A, Caporali L, Valentino ML, Carelli V. Mitochondrial diseases in adults. J Intern Med. 2020 Jun;287(6):592-608. doi: 10.1111/joim.13064.
PubMed 32463135Jeppesen TD, Schwartz M, Olsen DB, Wibrand F, Krag T, Duno M, Hauerslev S, Vissing J. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006 Dec;129(Pt 12):3402-12. doi: 10.1093/brain/awl149. Epub 2006 Jun 30.
PubMed 16815877Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrao ME, Jannig PR, Costa LA, Bacurau AV, Snijders T, Parise G, Tricoli V, Roschel H, Ugrinowitsch C. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol. 2016 Sep 15;594(18):5209-22. doi: 10.1113/JP272472. Epub 2016 Jul 9.
PubMed 27219125Cejudo P, Bautista J, Montemayor T, Villagomez R, Jimenez L, Ortega F, Campos Y, Sanchez H, Arenas J. Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve. 2005 Sep;32(3):342-50. doi: 10.1002/mus.20368.
PubMed 15962332Booth M. Assessment of physical activity: an international perspective. Res Q Exerc Sport. 2000 Jun;71 Suppl 2:114-20. doi: 10.1080/02701367.2000.11082794. No abstract available.
PubMed 25680021
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deciphering Muscle-Nerve Communication Via Mitochondrial Myopathy Insights: Exploring the Effects of Exercise Training
- ClinicalTrials.gov ID
- NCT07450690
- Acronym / sponsor ID
- MM-EX / H-25048935
- Conditions
- Mitochondrial Diseases, Mitochondrial Myopathy
- Keywords
- Exercise training, Mitochondrial function, Skeletal Muscle, Neuromuscular Junction, Muscle Plasticity
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 9 Jan 2026 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Oct 2030 (estimated)
- First posted
- 5 Mar 2026 (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.
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.
Detailed description
Mitochondrial dysfunction is a central contributor to skeletal muscle weakness, metabolic dysregulation, and reduced physical capacity in mitochondrial myopathies. Defects in mitochondrial oxidative phosphorylation impair energy production and trigger maladaptive cellular stress responses, contributing to progressive muscle deterioration. While structured exercise training has been shown to improve mitochondrial oxidative capacity and functional performance in individuals with mitochondrial myopathy, the cellular and molecular pathways driving these adaptations are not fully defined.
This study employs a within-subject, parallel-group, unilateral exercise training model to examine exercise-induced adaptations in skeletal muscle from adults with mitochondrial myopathy and matched healthy controls. Participants undergo a 3-4-week supervised unilateral aerobic interval training program consisting of 10 sessions, with the trained leg randomized and the contralateral leg serving as an internal untrained control. This design increases statistical power and allows direct comparison of trained versus untrained muscle within the same individual.
Comprehensive phenotyping is conducted before the intervention, including assessments of muscle strength, functional performance, body composition, physical activity, and maximal oxygen uptake. Skeletal muscle biopsies obtained from both legs following the intervention enable detailed evaluation of mitochondrial respiratory function, mitochondrial morphology, neuromuscular junction structure, protein synthesis, signaling pathways, and unbiased multi-omics analyses (proteomics, phosphoproteomics, metabolomics, lipidomics, and transcriptomics).
By integrating physiological, molecular, and structural outcomes, this study seeks to elucidate mechanisms by which exercise training may partially reverse mitochondrial and neuromuscular defects in mitochondrial myopathy and establish exercise as a targeted therapeutic strategy for mitochondrial dysfunction.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In a within-subject parallel-group longitudinal design, individuals with mitochondrial myopathy as well as matched controls sustain an exercise training intervention with one leg, while the contralateral leg serves as an inactive control.
| Arm | Type | Receives |
|---|---|---|
| Mitochondrial Myopathy | Experimental | Behavioral: Unilateral high-intensity interval training (HIIT)Individuals with myopathy caused by mutations in nuclear or mitochondrial DNA |
| Healthy controls | Active comparator | Behavioral: Unilateral high-intensity interval training (HIIT)Control subjects matched for age, sex and BMI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Known mtDNA or nuclear (nDNA) mutations
- Age above or equal to 18 years
- Age above or equal to 18 years
Key exclusion criteria (8 listed)
- 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
- Chronic medical conditions suspected to influence outcome measures
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 |
|---|---|---|
| Unilateral high-intensity interval training (HIIT)Participants will undergo ten sessions of HIIT of the leg randomized to the intervention while the inactive leg serves as the control leg | Behavioural | Healthy controls, Mitochondrial Myopathy |
Primary outcome
Muscle mitochondrial respiration
Time frame: 24-72 hours after final training session
Mitochondrial O2 flux is measured by high-resolution respirometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity
Muscle mitochondrial reactive oxygen species (ROS) production
Time frame: 24-72 hours after final training session
Mitochondrial H2O2 emission rates are measured by high-resolution fluorometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity
4 secondary outcomes
Muscle strength and endurance
Time frame: At first, fifth and tenth training session
Muscle structure and neuromuscular junction morphology
Time frame: 24-72 hours after final training session
Muscle integrated stress responses, growth and metabolic signaling
Time frame: 24-72 hours after final training session
Body and leg composition
Time frame: Baseline and 24-72 hours after final training session
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 5 Mar 2026.
- Background: PubMed 132082Saltin B, Nazar K, Costill DL, Stein E, Jansson E, Essen B, Gollnick D. The nature of the training response; peripheral and central adaptations of one-legged exercise. Acta Physiol Scand. 1976 Mar;96(3):289-305. doi: 10.1111/j.1748-1716.1976.tb10200.x.
- BackgroundPorcelli, S., Grassi, B., Poole, D.C., Marzorati, M., 2019. Exercise intolerance in patients with mitochondrial myopathies: perfusive and diffusive limitations in the O2 pathway. Current Opinion in Physiology 10, 202-209. https://doi.org/10.1016/j.cophys.2019.05.011
- Background: PubMed 18984605Murphy JL, Blakely EL, Schaefer AM, He L, Wyrick P, Haller RG, Taylor RW, Turnbull DM, Taivassalo T. Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain. 2008 Nov;131(Pt 11):2832-40. doi: 10.1093/brain/awn252.
- Background: PubMed 27396440MacInnis MJ, Zacharewicz E, Martin BJ, Haikalis ME, Skelly LE, Tarnopolsky MA, Murphy RM, Gibala MJ. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. 2017 May 1;595(9):2955-2968. doi: 10.1113/JP272570. Epub 2016 Aug 3.
- Background: PubMed 32463135La Morgia C, Maresca A, Caporali L, Valentino ML, Carelli V. Mitochondrial diseases in adults. J Intern Med. 2020 Jun;287(6):592-608. doi: 10.1111/joim.13064.
- Background: PubMed 16815877Jeppesen TD, Schwartz M, Olsen DB, Wibrand F, Krag T, Duno M, Hauerslev S, Vissing J. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006 Dec;129(Pt 12):3402-12. doi: 10.1093/brain/awl149. Epub 2006 Jun 30.
- Background: PubMed 27219125Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrao ME, Jannig PR, Costa LA, Bacurau AV, Snijders T, Parise G, Tricoli V, Roschel H, Ugrinowitsch C. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol. 2016 Sep 15;594(18):5209-22. doi: 10.1113/JP272472. Epub 2016 Jul 9.
- Background: PubMed 15962332Cejudo P, Bautista J, Montemayor T, Villagomez R, Jimenez L, Ortega F, Campos Y, Sanchez H, Arenas J. Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve. 2005 Sep;32(3):342-50. doi: 10.1002/mus.20368.
- Background: PubMed 25680021Booth M. Assessment of physical activity: an international perspective. Res Q Exerc Sport. 2000 Jun;71 Suppl 2:114-20. doi: 10.1080/02701367.2000.11082794. No abstract available.
- 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.
Lykke Sylow, Ass.prof contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Unilateral high-intensity interval training (HIIT) in people with Mitochondrial Diseases and Mitochondrial Myopathy, run by University of Copenhagen at 1 site in Denmark.
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 3 inclusion and 8 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 5 Mar 2026. 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 Denmark. 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 Tue L Nielsen, MD (+45 3545 8748, tue.leth.nielsen.01@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle mitochondrial respiration (time frame: 24-72 hours after final training session). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07450690, which also lists 9 linked publications.
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 5 Mar 2026.