About this trial

The goals of our research project are to identify factors explaining inter-individual variation in responses to resistance training (RT) and the baseline determinants underlying an individual's sensitivity to respond to RT. Moreover, investigators aim to assess whether a responsiveness to RT predicts responsiveness to endurance training (ET). Thus, investigators aim to gain a deeper understanding of exercise adaptation processes. The main questions investigators aim to answer are:

* Can the physiological responses of one RT intervention be extrapolated to a subsequent RT intervention? * If so, what are the mechanisms underlying differing skeletal muscle growth responses in low, and high responders of skeletal muscle hypertrophy? * If so, do the low responders of skeletal muscle growth respond more favourably when the amount of RT is increased? * Are the high, moderate, and low responders of RT also the highest, moderate, and lowest responders to ET?

To examine these main research questions, high (n=30), low (n=30), and moderate (n=30) responders of skeletal muscle growth in response to RT (intervention I, NCT05874986) are reallocated into a subsequent 12-week RT intervention (intervention II) after a detraining period. A subgroup of these participants (n=10) will engage in a 6-week control period before starting the second RT period. Additionally, after intervention II, participants will participate in an ET intervention, lasting 6 weeks.

In this intervention II, reallocated participants will be:

* Resistance training with supervision for 12 weeks * Consuming deuterium oxide for the assessment of muscle protein synthesis * Consuming D3-3-methylhistidine for the assessment of acute muscle protein breakdown * Consuming D3-creatine for the examination of whole-body skeletal muscle mass * Providing a spot urine sample six (6) times, and urine collection for 24 hours performed twice * Providing saliva samples (30-32 in total) for the assessment of body water enrichment of deuterium * Providing a muscle biopsy four or five (4-5) times during the study * Providing a blood sample fourteen (14) times during the study * Assessed for body composition and body volume four or five times (4-5) during the study * Participating in muscle size, maximal dynamic strength and TMS measurements four or five (4-5) times during the study * Asked to answer questionnaires related to e.g. stress, physical activity, sleep, perceived exertion, and diet * Participating in recovery measurements before and after the second-to-last and the last RT bout, and once in the days between these RT bouts, consisting of six (6) body volume measurements and six (6) maximal voluntary isometric contraction (kg) tests using horizontal leg press for the assessment of neuromuscular recovery * Participating in an acute resistance exercise (RE) after the 12-week RT intervention.

Furthermore, in the ET intervention, participants will be:

* Participating in a familiarization session and resting electrocardiograph measurements before the intervention * Participating in endurance testing consisting of body composition, movement economy, and incremental RAMP testing before and after ET intervention * Endurance training with supervision for 6 weeks, three times a week.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

age 18-50

healthy (e.g., no diagnosed type 2 diabetes, cardiovascular disease, musculoskeletal disorders, etc.)

prior participation in intervention I (NCT05874986)

Disqualifiers

medication affecting the cardiovascular system or metabolism

metabolic, musculoskeletal, cardiovascular, or other diseases or disorders which may preclude the ability to perform exercise training and testing

Trial design

Design model

Parallel

Treatments tested in this trial

Resistance Training
Other intervention
12-week resistance training

Treatment groups

90 Participants

are divided into 3 treatment groups

Group A: High responders (n=30)Experimental treatment 1 intervention

Group B: Moderate responders (n=30)Experimental treatment 1 intervention

Group C: Low Responders (n=30)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Change in m. vastus lateralis (VL) cross-sectional area (CSA) with ultrasound (US)

VL CSA (cm\^2) is determined at mid-thigh using a B-mode axial plane US (Venue Fit R4, GE Medical Systems, USA) with a L4-20t-RS linear-array probe (48,43 mm width) in extended-ﬁeld-of-view mode (6/12 MHz, 39 frames per second). Additionally, VL CSA (cm\^2) will also be determined at baseline with different US, at mid-thigh using a B-mode axial plane US (model SSD-α10, Aloka, Tokyo, Japan) with a 13 MHz linear-array probe (60 mm width) in extended-ﬁeld-of-view mode (23 Hz sampling frequency). Aloka-US was used in the intervention I, but GE-US in intervention II due to the progressive malfunctioning of Aloka. Therefore, both machines are used in baseline measurements to calculate the plausible inter-US variability. The CSA will be measured using the polygon function in ImageJ software. Per each measurement, three images will be analysed from which the average from the two closest ones will be calculated.

Time frame

Baseline (test and retest), week 7, week 13

Secondary outcomes

1

Muscle protein synthesis (MPS) with the Combined Oral Stable Isotope Assessment of Muscle (COSIAM)

A baseline saliva sample is collected to determine the deuterium labelling of plasma proteins. Then, participants ingest 3ml/kg deuterium oxide (D2O, 70-Atom%) divided into three boluses and 1 ml/kg top-up dose twice a week throughout the MPS examination period. When muscle proteins are built, the accumulation of deuterium-labelled alanine amino acid in the VL can be used to measure local fractional sarcoplasmic, myofibrillar, mitochondrial, and collagen MPS rates via gas chromatography-pyrolysis-isotope ratio mass spectrometry (GC-Pyrolysis-IRMS). The outcome will be expressed as %/day. 30 mg of VL muscle biopsy is used for MPS analysis. To estimate alanine precursor enrichment (APE), saliva samples are collected before and after each D2O drink consumption and 24 and 48 hours after the 3 x bolus to monitor body water enrichment via thermal conversion elemental analyser (TC/EA)-IRMS. Mass spectrometry analyses will be performed at the University of Nottingham, United Kingdom.

Time frame

From baseline to week 7 (6 weeks of RT in duration)

2

Muscle protein breakdown (MPB) with the Combined Oral Stable Isotope Assessment of Muscle (COSIAM)

Before each measurement day, participants ingest 10 mg of stable isotopically labelled D-3-methylhistidine (D-3-MH) dissolved in 50 millilitres of water. When muscle proteins containing D-3-MH are degraded, D-3-MH is released into circulation. As D-3-MH cannot be reused for protein synthesis, D-3-MH can be used as a biomarker for muscle protein breakdown (MPB). The enrichment of labelled D-3-MH is then measured from the blood samples to assess MPB. The outcome will be expressed as the tracer dilution (k) rate of D3-3-MH and measured with repeated plasma sampling. 20-24 hours after the ingestion of D3-3MH, five plasma samples will be collected within three hours, each separated by 45 minutes. Plasma samples will be analysed at the University of Nottingham, United Kingdom.

Time frame

Baseline, Week 7

3

Change in whole-body skeletal muscle mass (SMM) with the Combined Oral Stable Isotope Assessment of Muscle (COSIAM)

First, a baseline urine sample is collected to measure D3-creatinine enrichment. Then, after the bladder is empty, participants consume 30 mg of labelled D3-creatine dissolved in 50 millilitres of water. The amount of D-3 creatine that spills over in urine samples after 24 hours of ingestion will then be used to determine the amount of D-3 creatine retained in the body by 24-hour urine collection. Then, as the amount of creatine-to-creatinine conversion remains similar in the total muscle pool, the comparison of both non-labelled and labelled creatinine can be used to estimate the whole-body muscle creatine pool from the urine samples gathered 48 to 72 hours post-ingestion. This enables the calculation of whole-body skeletal muscle mass with a simple equation and the following outcome will be expressed as kilograms (kg). Urine samples will be analysed at the University of Nottingham, United Kingdom.

Time frame

Baseline, Week 7

4

Change in muscle thickness (MT) of the elbow flexors after 6 and 12-week resistance training

MT of m. biceps brachii and m. brachialis is measured using a B-mode axial plane ultrasound (Venue Fit R4, GE Medical Systems, USA) with a L4-20t-RS linear-array probe (48,43 mm width).

Time frame

Baseline (test and retest), week 7, week 13

Resistance Training, Detraining, and Retraining Study 2024 (TraDeRe2024)

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts