An observational study in Aging, sponsored by VU University of Amsterdam. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-06.
Sponsored by VU University of Amsterdam · Observational
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.
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.
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This study's planned enrollment of 60 is below the median of 98 across 1,235 observational studies indexed under Motor Activity.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
In order to be eligible to participate in this study, young sedentary participants must meet all of the following criteria:
In order to be eligible to participate in this study, young trained participants must meet all of the following criteria:
In order to be eligible to participate in this study, older sedentary participants must meet all of the following criteria:
In order to be eligible to participate in this study, older trained participants must meet all of the following criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
* 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
Other: Maximal exercise test · Other: 3D Ultrasound · Other: Dynamometry · Other: Exercise test and occlusions · Other: Exercise test in MRI · Procedure: Muscle biopsy
* 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
Other: Maximal exercise test · Other: 3D Ultrasound · Other: Dynamometry · Other: Exercise test and occlusions · Other: Exercise test in MRI · Procedure: Muscle biopsy
* 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
Other: Maximal exercise test · Other: 3D Ultrasound · Other: Dynamometry · Other: Exercise test and occlusions · Other: Exercise test in MRI · Procedure: Muscle biopsy
* 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
Other: Maximal exercise test · Other: 3D Ultrasound · Other: Dynamometry · Other: Exercise test and occlusions · Other: Exercise test in MRI · Procedure: Muscle biopsy
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.
Muscle volume and morphological characteristics will be assessed via 3D ultrasound imaging.
To determine the contractile properties of the knee extensors, participants will perform maximal isometric and isoinertial contractions of the knee extensors on a dynamometer.
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 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 \[31P-MRS\].
A muscle biopsy will be obtained from the vastus lateralis using a modified Bergström needle technique with suction.
Maximal oxygen uptake (V̇O2max)
ml/min/kg
Time frame: Baseline (visit 1)
Muscle volume
cm\^3
Time frame: Baseline (visit 1)
Muscle strength
Newton-metre (Nm)
Time frame: Baseline (visit 1)
Muscle power
Watt (W)
Time frame: Baseline (visit 1)
Muscle diffusing capacity for oxygen (DmO2)
Differences in recovery constant k (min-1) obtained under conditions of high, medium or low O2 availability
Time frame: Baseline (visit 1) and visit 2-4. In total 4 weeks.
Muscle mitochondrial fragmentation index (A.U.)
Degree of fragmentation of the mitochondrial pool.
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks).
Gas exchange and ventilatory variables (gas exchange threshold, respiratory compensation point, maximal ventilation)
L/min
Time frame: Baseline (visit 1)
(Peak) power output
Watt (W)
Time frame: Baseline (visit 1)
Mean response time of the V̇O2 slope during ramp exercise
sec
Time frame: Baseline (visit 1)
(Maximum) heart rate (HR)
beats per minute (bpm)
Time frame: Baseline (visit 1) and during visit 2-4 (max 4 weeks in total)
Maximal O2 pulse
ml/beat
Time frame: Baseline (visit 1)
Slope of ventilation (VE) versus carbon dioxide (VCO2) output during ramp exercise (i.e. ventilatory efficiency)
V̇E/V̇CO2 slope
Time frame: Baseline (visit 1)
V̇O2/HR slope during ramp exercise
beats/L/min
Time frame: Baseline (visit 1)
Maximal respiratory exchange ratio (RER)
RER = VCO2/VO2
Time frame: Baseline (visit 1)
Maximal ventilatory equivalents
VE/VCO2 and VE/VO2
Time frame: Baseline (visit 1)
Maximal end-tidal pressures for oxygen (O2) and carbon dioxide (CO2)
mmHg
Time frame: Baseline (visit 1)
Capillary lactate concentration
mmol/L
Time frame: Baseline (visit 1)
Maximal respiratory frequency
breaths/min
Time frame: Baseline (visit 1)
Pulmonary oxygen uptake - baseline and steady state V̇O2
L/min
Time frame: Baseline (visit 1) and visit 2-4 (max 4 weeks in total)
Pulmonary oxygen uptake kinetics - Phase II V̇O2 time constant and time delay
sec
Time frame: Visit 2-4 (max 4 weeks in total)
Pulmonary oxygen uptake kinetics - Phase II V̇O2 amplitude
L/min
Time frame: Visit 2-4 (max 4 weeks in total)
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.
Time frame: Baseline (visit 1) and visit 2-4 (max 4 weeks in total)
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.
Time frame: Baseline (visit 1)
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)
Time frame: Baseline (visit 1)
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
Time frame: Baseline (visit 1)
Muscle (de)oxygenation breakpoint during incremental exercise
Power output (W) and maximal oxygen uptake (L/min)
Time frame: Baseline (visit 1)
Rate constant of mV̇O2 recovery kinetics under conditions of high, medium and low O2 availability
sec
Time frame: Baseline (visit 1)
Muscle morphology - Fascicle length
cm
Time frame: Baseline (visit 1)
Muscle morphology - pennation angle
degrees
Time frame: Baseline (visit 1)
Muscle morphology - (effective) physiological cross-sectional area (PCSA)
cm2
Time frame: Baseline (visit 1)
Muscle morphology - vastus lateralis specific force
N/cm2
Time frame: Baseline (visit 1)
Muscle morphology - estimated muscle fiber number
PCSA/muscle fiber cross-sectional area
Time frame: Baseline (visit 1)
Adipose tissue thickness at the site of NIRS measurement
mm
Time frame: Baseline (visit 1)
Mitochondrial respiratory function (background, LEAK, N-linked respiration, OXPHOS, ETS, succinate (S) + rotenone (ROT)-linked uncoupled respiration, )
pmol/s/mg
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks).
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
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks).
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
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks).
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
Time frame: Visit 5 MRI
31P-MRS-derived mitochondrial bioenergetic function rate constant of PCr
Rate constant of Phosphocreatine \[PCr\] on- and off-kinetics (sec)
Time frame: Visit 5 MRI
31P-MRS-derived mitochondrial bioenergetic function - maximal rate of oxidative ATP synthesis
mM/s
Time frame: Visit 5 MRI
Muscle fiber type distribution
Type I, IIa, IIx and hybrid fiber-type proportions (%)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
(mean) fiber cross-sectional area, also fiber type specific
um
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Weighted fiber cross-sectional area
um2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Mean and fiber type specific succinate dehydrogenase activity
A660/um/s
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Integrated fiber succinate dehydrogenase activity
A660.um/s
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Mean and fiber type specific myoglobin concentrations
mM
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - capillary density
number of capillaries/mm2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - capillary-to-fiber ratio
capillary-to-fiber ratio
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - mean number of capillaries surrounding a fiber (CAF)
number of capillaries
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - mean number of capillaries surrounding a fiber in relation to fiber area (CAFA)
number of capillaries/um2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - capillary-to fiber-perimeter exchange index (CFPE)
CFPE (unitless)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - length of capillaries relative to fiber perimeter (LC/PF)
percentage (%)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
Muscle capillarization - sarcomere length
um
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - staining within time window of 2 years.
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
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - western blot within time window of 2 years.
Physical activity status - pedometer
Number of steps per day
Time frame: Baseline 7 days
Mitochondrial area density
Percentage (%)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - electron microscopy (EM) within time window of 2 years.
Mitochondrial volume density
um3.um3.10\^2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial number
number/um2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial area
um2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial height, width, perimeter and maximal+minimal Feret's diameter
um
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial surface area-to-volume ratio
um/um\^2
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial circularity
Circularity (AU)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial roundness
Roundness (AU)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial aspect ratio
Aspect ratio (AU)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
Mitochondrial cristae area density
Percentage (%)
Time frame: Visit 6 muscle biopsy (+/- after 4 weeks) - EM within time window of 2 years.
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Started Mar 2024 (actual). Primary completion is estimated for Dec 2025, 21 months after the start.
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VU University of Amsterdam