Exercise Training Effects on Muscle Function in Adults With Mitochondrial Myopathy

NCT07450690 | Recruiting

• 1 other identifier: H-25048935
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Mitochondrial Diseases; Mitochondrial Myopathy

Keywords

Exercise training; Mitochondrial function; Skeletal Muscle; Neuromuscular Junction; Muscle Plasticity

Outcome Measures

Primary Outcomes (2)

• 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

  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

  24-72 hours after final training session

Secondary Outcomes (4)

• Muscle strength and endurance

  At first, fifth and tenth training session

• Muscle structure and neuromuscular junction morphology

  24-72 hours after final training session

• Muscle integrated stress responses, growth and metabolic signaling

  24-72 hours after final training session

• Body and leg composition

  Baseline and 24-72 hours after final training session

Other Outcomes (1)

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

  24-72 hours after final training session

Study Arms (2)

Mitochondrial Myopathy

EXPERIMENTAL

Individuals with myopathy caused by mutations in nuclear or mitochondrial DNA

Behavioral: Unilateral high-intensity interval training (HIIT)

Healthy controls

ACTIVE COMPARATOR

Control subjects matched for age, sex and BMI

Behavioral: Unilateral high-intensity interval training (HIIT)

Interventions

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

Healthy controls; Mitochondrial Myopathy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Known mtDNA or nuclear (nDNA) mutations
• Age above or equal to 18 years

You may not qualify if:

• 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
• Age above or equal to 18 years
• 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

Sponsors & Collaborators

• University of Copenhagen: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

University of Copenhagen, Dept of Biomedical Sciences

Copenhagen, DK-2100, Denmark

RECRUITING

Related Publications (9)

• Saltin, B., Nazar, K., Costill, D.L., Stein, E., Jansson, E., Essén, B., Gollnick, P.D., 1976. The Nature of the Training Response; Peripheral and Central Adaptations to One-Legged Exercise. Acta Physiologica Scandinavica 96, 289-305. https://doi.org/10.1111/j.1748-1716.1976.tb10200.x

  BACKGROUND

• Porcelli, 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

• Murphy, J.L., Blakely, E.L., Schaefer, A.M., He, L., Wyrick, P., Haller, R.G., Taylor, R.W., Turnbull, D.M., Taivassalo, T., 2008. Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain 131, 2832-2840. https://doi.org/10.1093/brain/awn252

  BACKGROUND

• MacInnis, M.J., Zacharewicz, E., Martin, B.J., Haikalis, M.E., Skelly, L.E., Tarnopolsky, M.A., Murphy, R.M., Gibala, M.J., 2017b. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol 595, 2955-2968. https://doi.org/10.1113/JP272570

  BACKGROUND

• La Morgia, C., Maresca, A., Caporali, L., Valentino, M.L., Carelli, V., 2020. Mitochondrial diseases in adults. Journal of Internal Medicine 287, 592-608. https://doi.org/10.1111/joim.13064

  BACKGROUND

• Jeppesen, T.D., Schwartz, M., Olsen, D.B., Wibrand, F., Krag, T., Duno, M., Hauerslev, S., Vissing, J., 2006. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain 129, 3402-3412. https://doi.org/10.1093/brain/awl149

  BACKGROUND

• Damas, F., Phillips, S.M., Libardi, C.A., Vechin, F.C., Lixandrão, M.E., Jannig, P.R., Costa, L.A.R., Bacurau, A. V., Snijders, T., Parise, G., Tricoli, V., Roschel, H., Ugrinowitsch, C., 2016. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. Journal of Physiology 594, 5209-5222. https://doi.org/10.1113/JP272472

  BACKGROUND

• Cejudo, P., Bautista, J., Montemayor, T., Villagómez, R., Jiménez, L., Ortega, F., Campos, Y., Sánchez, H., Arenas, J., 2005. Exercise training in mitochondrial myopathy: A randomized controlled trial. Muscle Nerve 32, 342-350. https://doi.org/10.1002/mus.20368

  BACKGROUND

• Booth, M., 2000. Assessment of Physical Activity: An International Perspective. Research Quarterly for Exercise and Sport 71, 114-120. https://doi.org/10.1080/02701367.2000.11082794

  BACKGROUND

MeSH Terms

Conditions

Mitochondrial Diseases; Mitochondrial Myopathies

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Tue L Nielsen, MD

CONTACT

+45 3545 8748; tue.leth.nielsen.01@regionh.dk

Lykke Sylow, Ass.prof

CONTACT

lykkesylow@sund.ku.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, group leader

Model Details: 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.

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: March 5, 2026
• Study Start: January 9, 2026
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2030
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)