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AgingAGAMEMNONNCT06539078

Skeletal Muscle Mitochondria in Ageing

An observational study of Aging, run by VU University of Amsterdam at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Healthy ageing is associated with the loss of muscle mass and physical function. As a result, older people are limited in their independence. The aging of muscles typically begins around the age of 30. From this age onward, muscle strength, muscle mass, and the maximum oxygen uptake of muscles decrease. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Aging
What is being tested?
Maximal exercise test, 3D Ultrasound and Dynamometry
Type of treatment
Surgery or procedure
How many people
60 participants
Where
1 siteNetherlands
Study dates
25 Mar 2024to Dec 2026
Phase
Observational
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 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: 15 sedentary and 15 endurance-trained young and middle-aged individuals will be recruited per age group (i.e. a total of 60 individuals spanning 4 groups). An equal balance of the sexes will be aimed for in each group. All participants will be recruited from specific social media groups, through personal networks of friends, family and colleagues, flyers and posters at local sports clubs and on the VU Campus. All testing will be conducted at the VU or in the Department of Radiology and Nuclear Medicine at Amsterdam UMC location AMC. Therefore, participants should be currently residing in or willing to travel to Amsterdam.

Who may be able to join

  • In order to be eligible to participate in this study, young sedentary participants must meet all of the following criteria:
  • Aged between 18-30 years
  • Male or female
  • Not currently engaging in any formal exercise training or competitive sports
  • No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
  • In order to be eligible to participate in this study, young trained participants must meet all of the following criteria:
Show all 20Show fewer
  • Aged between 18-30 years
  • Male or female
  • Currently engaging in formal training (at least 3 times per week) in competitive endurance sports
  • No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
  • In order to be eligible to participate in this study, older sedentary participants must meet all of the following criteria:
  • Aged between 50-65 years
  • Male or female
  • Not currently engaging in any formal exercise training or competitive sports
  • No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
  • In order to be eligible to participate in this study, older trained participants must meet all of the following criteria:
  • Aged between 50-65 years
  • Male or female
  • Currently engaging in formal training (at least 3 times per week) in competitive endurance sports
  • No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

Who cannot join

  • Age that falls outside of 18-30 years (young groups) or 50-65 years (middle-aged groups)
  • Inability to provide informed consent
  • History of claustrophobia
  • Ineligibility to perform the exercise test described in this study protocol or follow instructions
  • Taking any medications known to interfere with the physiological responses to exercise, e.g. e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 receptor agonists
  • Contraindication for MRI (e.g. pacemaker, claustrophobia)
Show all 10Show fewer
  • Being under investigation for non-diagnosed disease at the time of investigation
  • Body Mass Index (BMI) >30 due to adiposity, since this is known to cause difficulties in obtaining muscle biopsies and NIRS measurements
  • Pregnancy
  • Are current smokers or have been a regular smoker within the last 12 months

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ellen Breedveld, MSc contact

+31636318844

e.a.breedveld@vu.nl

Netherlands1 site, 1 recruiting

  • Vrije Universiteit Amsterdam

    Amsterdam, North Holland, 1081HV

    Ellen Breedveld, MSc, +31636318844, e.a.breedveld@vu.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Exercise as a Countermeasure Against the Effects of Ageing on Muscle Mitochondria, Diffusive Oxygen Transport and Muscle Volume

Healthy ageing is associated with the loss of muscle mass and physical function. As a result, older people are limited in their independence. The aging of muscles typically begins around the age of 30. From this age onward, muscle strength, muscle mass, and the maximum oxygen uptake of muscles decrease. The reasons for this are not entirely clear, but it seems to be partly related to how oxygen moves from our blood vessels to the muscles and how muscles burn energy. The precise role of age and physical fitness, as well as whether exercise can counteract the effects of ageing, is still unknown. Therefore, in this study, we aim to investigate the muscle function of both physically active and inactive young and middle-aged individuals. We hypothesise that endurance training can mitigate some of the effects of ageing.

Read the detailed description

Healthy ageing is associated with a loss of muscle mass and physical function. This loss of physical function is underpinned by reductions in characteristics such as muscle strength, power, and maximal oxygen uptake (V̇O2max; reflecting exercise capacity). However, the causal contributors to these age-associated impairments, and the role of exercise training status in mitigating them, remain poorly defined. Skeletal muscle mitochondrial function has been proposed to be a key contributor to age-associated effects on physical function, however many conflicting results are present in the extant human literature. Moreover, diffusion of oxygen from capillaries to mitochondria is a key determinant of V̇O2max, however, whether the skeletal muscle diffusive capacity for oxygen (DmO2) declines with age is unknown. A new technique utilizing near-infrared spectroscopy (NIRS) will enable the non-invasive assessment of skeletal muscle diffusive capacity in young and elderly subjects for the first time to resolve this issue. The primary aims of this study are therefore to 1) compare DmO2 derived via NIRS between young sedentary, young endurance-trained, older sedentary, and older endurance-trained subjects; 2) to compare non-invasive (i.e. with NIRS and 31phosphorous magnetic resonance spectroscopy [31P-MRS]) and invasive (i.e. measures of mitochondrial morphology and respiration obtained by skeletal muscle biopsy) markers of mitochondrial function between the same groups, and 3) to assess the relationships between DmO2, mitochondrial measures and assessments of capillarization with functional measurements of muscle strength, power, and V̇O2max.

Conditions
Aging
Being tested
Maximal exercise test, 3D Ultrasound, Dynamometry, Exercise test and occlusions, Exercise test in MRI
Keywords
Exercise, Mitochondria, Skeletal muscle
Medical subject headings
Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Maximal exercise testOther

    Participants will undertake an incremental ramp test on a cycle ergometer to determine maximal oxygen uptake (V̇O2max) and the gas exchange threshold (GET). Throughout the exercise test, muscle oxygenation and deoxygenation will be monitored by NIRS.

  • 3D UltrasoundOther

    Muscle volume and morphological characteristics will be assessed via 3D ultrasound imaging.

  • DynamometryOther

    To determine the contractile properties of the knee extensors, participants will perform maximal isometric and isoinertial contractions of the knee extensors on a dynamometer.

  • Exercise test and occlusionsOther

    Participants will perform a series of moderate-intensity constant power output exercise bouts on a cycle ergometer following which the recovery rates of muscle V̇O2 will be determined via a series of intermittent arterial occlusions. Throughout all tests, pulmonary gas exchange and ventilation will be determined and muscle oxygenation and deoxygenation will be monitored by NIRS.

  • Exercise test in MRIOther

    Exercise will be performed on a custom-built magnetic resonance-compatible cycle ergometer in supine position for determination of muscle phosphocreatine recovery kinetics using 31phosphorous magnetic resonance spectroscopy [31P-MRS].

  • Muscle biopsyProcedure or surgery

    A muscle biopsy will be obtained from the vastus lateralis using a modified Bergström needle technique with suction.

Study groups in NCT06539078
Study groupRoleWhat they receive
Young, sedentary participants* Aged between 18-30 years * Male or female * Not currently engaging in any formal exercise training or competitive sports * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
Receives: Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy
Young endurance-trained participants* Aged between 18-30 years * Male or female * Currently engaging in formal training (at least 3 times per week) in competitive endurance sports (i.e. running, cycling, swimming, triathlon, etc.) * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
Receives: Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy
Middle-aged, sedentary participants* Aged between 50-65 years * Male or female * Not currently engaging in any formal exercise training or competitive sports * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
Receives: Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy
Middle-aged endurance-trained participants* Aged between 50-65 years * Male or female * Currently engaging in formal training (at least 3 times per week) in competitive endurance sports (i.e. running, cycling, swimming, triathlon, etc.) * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
Receives: Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal oxygen uptake (V̇O2max)

    ml/min/kg

    Measured: Baseline (visit 1)

  2. Muscle volume

    cm^3

    Measured: Baseline (visit 1)

  3. Muscle strength

    Newton-metre (Nm)

    Measured: Baseline (visit 1)

  4. Muscle power

    Watt (W)

    Measured: Baseline (visit 1)

  5. Muscle diffusing capacity for oxygen (DmO2)

    Differences in recovery constant k (min-1) obtained under conditions of high, medium or low O2 availability

    Measured: Baseline (visit 1) and visit 2-4. In total 4 weeks.

  6. Muscle mitochondrial fragmentation index (A.U.)

    Degree of fragmentation of the mitochondrial pool.

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks).

Secondary outcomes (58)

  1. Gas exchange and ventilatory variables (gas exchange threshold, respiratory compensation point, maximal ventilation)

    L/min

    Measured: Baseline (visit 1)

  2. (Peak) power output

    Watt (W)

    Measured: Baseline (visit 1)

  3. Mean response time of the V̇O2 slope during ramp exercise

    sec

    Measured: Baseline (visit 1)

  4. (Maximum) heart rate (HR)

    beats per minute (bpm)

    Measured: Baseline (visit 1) and during visit 2-4 (max 4 weeks in total)

  5. Maximal O2 pulse

    ml/beat

    Measured: Baseline (visit 1)

  6. Slope of ventilation (VE) versus carbon dioxide (VCO2) output during ramp exercise (i.e. ventilatory efficiency)

    V̇E/V̇CO2 slope

    Measured: Baseline (visit 1)

  7. V̇O2/HR slope during ramp exercise

    beats/L/min

    Measured: Baseline (visit 1)

  8. Maximal respiratory exchange ratio (RER)

    RER = VCO2/VO2

    Measured: Baseline (visit 1)

  9. Maximal ventilatory equivalents

    VE/VCO2 and VE/VO2

    Measured: Baseline (visit 1)

  10. Maximal end-tidal pressures for oxygen (O2) and carbon dioxide (CO2)

    mmHg

    Measured: Baseline (visit 1)

  11. Capillary lactate concentration

    mmol/L

    Measured: Baseline (visit 1)

  12. Maximal respiratory frequency

    breaths/min

    Measured: Baseline (visit 1)

  13. Pulmonary oxygen uptake - baseline and steady state V̇O2

    L/min

    Measured: Baseline (visit 1) and visit 2-4 (max 4 weeks in total)

  14. Pulmonary oxygen uptake kinetics - Phase II V̇O2 time constant and time delay

    sec

    Measured: Visit 2-4 (max 4 weeks in total)

  15. Pulmonary oxygen uptake kinetics - Phase II V̇O2 amplitude

    L/min

    Measured: Visit 2-4 (max 4 weeks in total)

  16. Concentrations of NIRS derived muscle oxy- and deoxygenated [haemoglobin + myoglobin] (HbO2, Hbb) and tissue saturation index (TSI).

    HbO2 and Hbb: % maximal value, TSI (%) = HbO2/(HbO2+Hbb) For all variables resting concentration, baseline cycling concentration, (sub)maximal exercise concentration will be reported.

    Measured: Baseline (visit 1) and visit 2-4 (max 4 weeks in total)

  17. NIRS derived muscle oxy- and deoxygenated [haemoglobin + myoglobin] (HbO2, Hbb) and tissue saturation index (TSI) versus relative and absolute work rate.

    HbO2 and Hbb: % maximal value, TSI (%) = HbO2/(HbO2+Hbb) versus relative (%max) and absolute power output (W) Relative and absolute work rates comparisons will be reported for all variables: resting concentration, baseline cycling concentration, (sub)maximal exercise concentration.

    Measured: Baseline (visit 1)

  18. Initial and secondary slope of increase during incremental exercise will be reported for NIRS derived muscle oxy- and deoxygenated [haemoglobin + myoglobin] (HbO2, Hbb) and tissue saturation index (TSI) versus relative work rate.

    concentration[Hbb/HbO2/TSI]%/delta%peak power(W)

    Measured: Baseline (visit 1)

  19. Initial and secondary slope during incremental exercise will be reported for NIRS derived muscle oxy- and deoxygenated [haemoglobin + myoglobin] (HbO2, Hbb) and tissue saturation index (TSI) versus absolute work rate.

    concentration[Hbb/HbO2/TSI]%/deltaW

    Measured: Baseline (visit 1)

  20. Muscle (de)oxygenation breakpoint during incremental exercise

    Power output (W) and maximal oxygen uptake (L/min)

    Measured: Baseline (visit 1)

  21. Rate constant of mV̇O2 recovery kinetics under conditions of high, medium and low O2 availability

    sec

    Measured: Baseline (visit 1)

  22. Muscle morphology - Fascicle length

    cm

    Measured: Baseline (visit 1)

  23. Muscle morphology - pennation angle

    degrees

    Measured: Baseline (visit 1)

  24. Muscle morphology - (effective) physiological cross-sectional area (PCSA)

    cm2

    Measured: Baseline (visit 1)

  25. Muscle morphology - vastus lateralis specific force

    N/cm2

    Measured: Baseline (visit 1)

  26. Muscle morphology - estimated muscle fiber number

    PCSA/muscle fiber cross-sectional area

    Measured: Baseline (visit 1)

  27. Adipose tissue thickness at the site of NIRS measurement

    mm

    Measured: Baseline (visit 1)

  28. Mitochondrial respiratory function (background, LEAK, N-linked respiration, OXPHOS, ETS, succinate (S) + rotenone (ROT)-linked uncoupled respiration, )

    pmol/s/mg

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks).

  29. Respiratory control ratios

    OXPHOS/ETS, LEAK/ETS, LEAK/OXPHOS, LEAK/NADH-linked, ROT+S/ETS, (OXPHOS-LEAK)/ETS, (OXPHOS-LEAK)/OXPHOS, (ETS-LEAK)/ETS, (ETS-OXPHOS)/ETS

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks).

  30. Intrinsic mitochondrial respiration (each respiratory state outlined below will be normalised to mitochondrial volume density)

    (pmol/s/mg)/mitochondrial area density (%) For: background, LEAK, N-linked respiration, OXPHOS, ETS, succinate + rotenone-linked uncoupled respiration

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks).

  31. 31P-MRS-derived mitochondrial bioenergetic function - resting and steady-state exercising concentrations and amplitude of exercise-induced changes of skeletal muscle Phosphocreatine [PCr], [inorganic phosphate] and pH

    mM pH = unitless

    Measured: Visit 5 MRI

  32. 31P-MRS-derived mitochondrial bioenergetic function rate constant of PCr

    Rate constant of Phosphocreatine [PCr] on- and off-kinetics (sec)

    Measured: Visit 5 MRI

  33. 31P-MRS-derived mitochondrial bioenergetic function - maximal rate of oxidative ATP synthesis

    mM/s

    Measured: Visit 5 MRI

  34. Muscle fiber type distribution

    Type I, IIa, IIx and hybrid fiber-type proportions (%)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  35. (mean) fiber cross-sectional area, also fiber type specific

    um

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  36. Weighted fiber cross-sectional area

    um2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  37. Mean and fiber type specific succinate dehydrogenase activity

    A660/um/s

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  38. Integrated fiber succinate dehydrogenase activity

    A660.um/s

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  39. Mean and fiber type specific myoglobin concentrations

    mM

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  40. Muscle capillarization - capillary density

    number of capillaries/mm2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  41. Muscle capillarization - capillary-to-fiber ratio

    capillary-to-fiber ratio

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  42. Muscle capillarization - mean number of capillaries surrounding a fiber (CAF)

    number of capillaries

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  43. Muscle capillarization - mean number of capillaries surrounding a fiber in relation to fiber area (CAFA)

    number of capillaries/um2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  44. Muscle capillarization - capillary-to fiber-perimeter exchange index (CFPE)

    CFPE (unitless)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  45. Muscle capillarization - length of capillaries relative to fiber perimeter (LC/PF)

    percentage (%)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  46. Muscle capillarization - sarcomere length

    um

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.

  47. Mitochondrial dynamics proteins (Mfn1, Mfn2, OPA1, Drp1, Parkin, PINK1, Fis1, MTFP1, NRF1&2, PGC1a, TFAM, OXPHOS protein content (complexes I-V and total protein content)

    ug/mg loaded sample

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - western blot within time window of 2 years.

  48. Physical activity status - pedometer

    Number of steps per day

    Measured: Baseline 7 days

  49. Mitochondrial area density

    Percentage (%)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - electron microscopy (EM) within time window of 2 years.

  50. Mitochondrial volume density

    um3.um3.10^2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  51. Mitochondrial number

    number/um2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  52. Mitochondrial area

    um2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  53. Mitochondrial height, width, perimeter and maximal+minimal Feret's diameter

    um

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  54. Mitochondrial surface area-to-volume ratio

    um/um^2

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  55. Mitochondrial circularity

    Circularity (AU)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  56. Mitochondrial roundness

    Roundness (AU)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  57. Mitochondrial aspect ratio

    Aspect ratio (AU)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

  58. Mitochondrial cristae area density

    Percentage (%)

    Measured: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2024
  2. Study start25 Mar 2024
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06539078
Sponsor's protocol ID
2023.0746
Acronym
AGAMEMNON
Status last verified
Aug 2024
First submitted
18 Jul 2024
Last updated
6 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

An observational study of Aging, run by VU University of Amsterdam at 1 site in Netherlands.

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 20 inclusion and 10 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 6 Aug 2024. 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 Netherlands. 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 Ellen Breedveld, MSc (+31636318844, e.a.breedveld@vu.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal oxygen uptake (V̇O2max) (time frame: Baseline (visit 1)). The study lists 6 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 NCT06539078.

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 6 Aug 2024; AzTrials last refreshed its copy on 31 Oct 2026.

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