ContraTRAIN - a Validation Study of Contralateral Training Protocols

Study Overview
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Brief Summary
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This study aims to validate the use of contralateral designs in studies of effects of resistance exercise. It will recruit healthy young (18-35 years) individuals, which will be allocated to 4 experimental groups. In two of the experimental groups, 3x10 or 6x10 repetitions of heavy resistance exercise on one leg will be combined with no training of the other leg for 7 weeks. In the third group, 3x10 repetitions of heavy resistance exercise on one leg will be combined with 6x10 repetitions of heavy resistance exercise on the other leg for 7 weeks. In the fourth group, which serves as a control group, a period of no training (similar in length to the training period of groups 1-3; 7 weeks), before both legs will train 3x10 repetitions of heavy resistance exercise in an unilateral manner.

Detailed Description
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Our understanding of how exercise affects muscular adaptations at the cellular and molecular level comes from the use of skeletal muscle biopsies. Such studies are met by several challenges, including its invasive nature, costs of muscle analyses, large inter-participant variability in response to exercise and a limited number of subjects (related to ethical concerns regarding exposing participants to biopsies). Consequently, studies often include small sample sizes, resulting in low statistical power. This poses a great challenge to the field of exercise physiology. While increasing sample size may not always be feasible, employing alternative designs may offer a way to increase the statistical power. An example of such a design is the so-called cross-over design, wherein participants serve as their own control thereby reducing the inter-participant variation. An interesting variant of the cross-over design is the unilateral or contralateral exercise model. In such designs, each of the participant's limbs (e.g. legs) are randomly allocated to perform different types of training/treatments in close temporal proximity. This design obliterates the need for a wash-out period and removes the potential effects of confounding factors such as diet, activity and sleep decreases. Thus, resources, time spent and variability can be reduced. However, validation of such studies is lacking. In an effort to validate a contralateral training design, the investigators will recruit young (18-35 years) healthy individuals to 4 groups performing unilateral progressive strength training; (1) one leg with no training and one leg with 3x10 maximal repetitions, (2) one leg with no training and one leg with 6x10 maximal repetitions, (3) one leg with 3x10 maximal repetitions and one leg with 6x10 maximal repetitions and (4) a control group with an initial period of no training (similar in length to the training period of groups 1-3) followed by a period of 3x10 maximal repetitions on each leg. Leg training will consist of one-legged leg press and one-legged knee extensions. All groups, except the control group (during the no-training control period), will train the upper body by 3x10 maximal repetitions in bench press and lying rowing. Prior to the 7 week training intervention, all four groups will go through a 3-week period of familiarization to training and repeated testing (4 test time points for performance measures). This design allows us to investigate the benefits of a contralateral design compared to the more common two-group design, the intra-individual variation vs the inter-individual variation, the potential contralateral effect of training one leg on the physiology and functional abilities of the non-trained leg, and whether or not these perspective are affected by training volume. We will also investigate whether participant classification into low or high responders is universal across several measures of muscle mass and strength, and between different training volumes. Further, by measuring several hypertrophy-related outcomes (e.g. changes in ribosome volume, activation of satellite cells and transcriptional changes), the investigators will extend previous findings regarding the effects of training volume on these variables and their ability to predict training outcomes.

Official Title
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ContraTRAIN - a Validation Study of Contralateral Training Protocols

Conditions
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Healthy

Intervention / Treatment
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* Other: Strength training 3x10RM + no training
* Other: Strength training 6x10RM + no training
* Other: 3x10RM + 6x10RM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Exclusion Criteria: Smoking Strength training more than 2 times per months for the last 6 months Endurance training more than 3 hours per week Adverse reactions to lidocaine Consumption of supplements or medication affecting muscular adaptations to strength training

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3x10RM + no training<br> | Other: Strength training 3x10RM + no training<br>* Progressive unilateral strength training 3 times per week for 3 + 7 weeks. One leg exercises with 3 sets of 10 maximal repetitions, the other leg does not exercise.<br>|
| Experimental: 6x10RM + no training<br> | Other: Strength training 6x10RM + no training<br>* Progressive unilateral strength training 3 times per week for 3 + 7 weeks. One leg exercises with 6 sets of 10 maximal repetitions, the other leg does not exercise.<br>|
| Experimental: 3x10RM + 6x10RM<br> | Other: 3x10RM + 6x10RM<br>* Progressive unilateral strength training 3 times per week for 3 + 7 weeks. One leg exercises with 3 sets of 10 maximal repetitions, the other leg exercises with 6 sets of 10 maximal repetitions.<br>|
| No Intervention: Control<br>This arm includes 3 weeks of testing and 7 weeks of no intervention and post tests, followed by 7 weeks of progressive unilateral strength training 3 times per week for 7 weeks. Both legs exercises individually with 3 sets of 10 maximal repetitions. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle fiber area | Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry | Changes over the course of the intervention (0-10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass composition | Body mass composition measured using Dual-energy X-ray absorptiometry (DXA) | Changes over the course of the intervention (0-10 weeks) | 
| Rate of muscle protein synthesis (%/day) | By ingesting deuterium we will label alanine to measure the rate of its incorporation into muscle proteins. This is done by collection of blood before, during and after, and a biopsy 3 days after deuterium ingestion to be analyzed with chromatography and mass spectrometry. Results will be reported as a rate of synthesis in %/day. | Mesured over 3 days in week 7 of the study | 
| M. vastus lateralis thickness | M. vastus lateralis thickness mesured by ultrasound | Changes over the course of the intervention (0-10 weeks) | 
| Unilateral leg press strength (1RM test) | The ability of muscles of the lower body to exert maximal force during dynamic movements in a leg press | Changes over the course of the intervention (0-10 weeks) | 
| Unilateral knee extension strength (1RM test) | The ability of muscles of the lower body to exert maximal force during dynamic movements in a knee extension | Changes over the course of the intervention (0-10 weeks) | 
| Barbell bench press muscle strength (1RM test) | The ability of muscles of the upper body to exert maximal force during dynamic movements in a bench press | Changes over the course of the intervention (0-10 weeks) | 
| Lying rowing muscle strength (1RM test) | The ability of muscles of the upper body to exert maximal force during dynamic movements in a lying row exercise | Changes over the course of the intervention (0-10 weeks) | 
| Unilateral lower body isokinetic muscle strength at 60 and 240 deg per second in a mechanical dynamometer (Humac NORM) | The ability of muscles of the lower body to exert maximal force during isokinetic movements | Changes over the course of the intervention (0-10 weeks) | 
| Unilateral lower body isometric muscle strength in a mechanical dynamometer (Humac NORM) | The ability of muscles of the lower body to exert maximal force during isometric contractions | Changes over the course of the intervention (0-10 weeks) | 
| One-legged cycling | Performance indicies measured during an incremental one-legged cycling test | Changes over the course of the intervention (0-10 weeks) | 
| Muscle phenotype | Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry | Changes over the course of the intervention (0-10 weeks) | 
| Muscle cell biological traits | Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry | Changes over the course of the intervention (0-10 weeks) | 
| Gene expression in skeletal muscle | RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome | Changes over the course of the intervention (0-10 weeks) | 
| Protein abundances in skeletal muscle measured by western blot | Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome | Changes over the course of the intervention (0-10 weeks) | 
| Hormones in blood | Levels of hormones in blood | Changes over the course of the intervention (0-10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contralateral, Strength training, Muscle