<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03795025</url>
  </required_header>
  <id_info>
    <org_study_id>Trainome 2019#014</org_study_id>
    <nct_id>NCT03795025</nct_id>
  </id_info>
  <brief_title>ContraTRAIN - a Validation Study of Contralateral Training Protocols</brief_title>
  <official_title>ContraTRAIN - a Validation Study of Contralateral Training Protocols</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Inland Norway University of Applied Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Inland Norway University of Applied Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to validate the use of contralateral designs in studies of effects of&#xD;
      resistance exercise. It will recruit healthy young (18-35 years) individuals, which will be&#xD;
      allocated to 4 experimental groups. In two of the experimental groups, 3x10 or 6x10&#xD;
      repetitions of heavy resistance exercise on one leg will be combined with no training of the&#xD;
      other leg for 7 weeks. In the third group, 3x10 repetitions of heavy resistance exercise on&#xD;
      one leg will be combined with 6x10 repetitions of heavy resistance exercise on the other leg&#xD;
      for 7 weeks. In the fourth group, which serves as a control group, a period of no training&#xD;
      (similar in length to the training period of groups 1-3; 7 weeks), before both legs will&#xD;
      train 3x10 repetitions of heavy resistance exercise in an unilateral manner.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our understanding of how exercise affects muscular adaptations at the cellular and molecular&#xD;
      level comes from the use of skeletal muscle biopsies. Such studies are met by several&#xD;
      challenges, including its invasive nature, costs of muscle analyses, large inter-participant&#xD;
      variability in response to exercise and a limited number of subjects (related to ethical&#xD;
      concerns regarding exposing participants to biopsies). Consequently, studies often include&#xD;
      small sample sizes, resulting in low statistical power. This poses a great challenge to the&#xD;
      field of exercise physiology. While increasing sample size may not always be feasible,&#xD;
      employing alternative designs may offer a way to increase the statistical power. An example&#xD;
      of such a design is the so-called cross-over design, wherein participants serve as their own&#xD;
      control thereby reducing the inter-participant variation. An interesting variant of the&#xD;
      cross-over design is the unilateral or contralateral exercise model. In such designs, each of&#xD;
      the participant's limbs (e.g. legs) are randomly allocated to perform different types of&#xD;
      training/treatments in close temporal proximity. This design obliterates the need for a&#xD;
      wash-out period and removes the potential effects of confounding factors such as diet,&#xD;
      activity and sleep decreases. Thus, resources, time spent and variability can be reduced.&#xD;
      However, validation of such studies is lacking.&#xD;
&#xD;
      In an effort to validate a contralateral training design, the investigators will recruit&#xD;
      young (18-35 years) healthy individuals to 4 groups performing unilateral progressive&#xD;
      strength training; (1) one leg with no training and one leg with 3x10 maximal repetitions,&#xD;
      (2) one leg with no training and one leg with 6x10 maximal repetitions, (3) one leg with 3x10&#xD;
      maximal repetitions and one leg with 6x10 maximal repetitions and (4) a control group with an&#xD;
      initial period of no training (similar in length to the training period of groups 1-3)&#xD;
      followed by a period of 3x10 maximal repetitions on each leg. Leg training will consist of&#xD;
      one-legged leg press and one-legged knee extensions. All groups, except the control group&#xD;
      (during the no-training control period), will train the upper body by 3x10 maximal&#xD;
      repetitions in bench press and lying rowing. Prior to the 7 week training intervention, all&#xD;
      four groups will go through a 3-week period of familiarization to training and repeated&#xD;
      testing (4 test time points for performance measures).&#xD;
&#xD;
      This design allows us to investigate the benefits of a contralateral design compared to the&#xD;
      more common two-group design, the intra-individual variation vs the inter-individual&#xD;
      variation, the potential contralateral effect of training one leg on the physiology and&#xD;
      functional abilities of the non-trained leg, and whether or not these perspective are&#xD;
      affected by training volume. We will also investigate whether participant classification into&#xD;
      low or high responders is universal across several measures of muscle mass and strength, and&#xD;
      between different training volumes. Further, by measuring several hypertrophy-related&#xD;
      outcomes (e.g. changes in ribosome volume, activation of satellite cells and transcriptional&#xD;
      changes), the investigators will extend previous findings regarding the effects of training&#xD;
      volume on these variables and their ability to predict training outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Actual">March 12, 2020</completion_date>
  <primary_completion_date type="Actual">March 12, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Muscle fiber area</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body mass composition</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Body mass composition measured using Dual-energy X-ray absorptiometry (DXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of muscle protein synthesis (%/day)</measure>
    <time_frame>Mesured over 3 days in week 7 of the study</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>M. vastus lateralis thickness</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>M. vastus lateralis thickness mesured by ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unilateral leg press strength (1RM test)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the lower body to exert maximal force during dynamic movements in a leg press</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unilateral knee extension strength (1RM test)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the lower body to exert maximal force during dynamic movements in a knee extension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barbell bench press muscle strength (1RM test)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the upper body to exert maximal force during dynamic movements in a bench press</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lying rowing muscle strength (1RM test)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the upper body to exert maximal force during dynamic movements in a lying row exercise</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unilateral lower body isokinetic muscle strength at 60 and 240 deg per second in a mechanical dynamometer (Humac NORM)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the lower body to exert maximal force during isokinetic movements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unilateral lower body isometric muscle strength in a mechanical dynamometer (Humac NORM)</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>The ability of muscles of the lower body to exert maximal force during isometric contractions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>One-legged cycling</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Performance indicies measured during an incremental one-legged cycling test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle phenotype</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle cell biological traits</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression in skeletal muscle</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein abundances in skeletal muscle measured by western blot</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hormones in blood</measure>
    <time_frame>Changes over the course of the intervention (0-10 weeks)</time_frame>
    <description>Levels of hormones in blood</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>3x10RM + no training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>6x10RM + no training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>3x10RM + 6x10RM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Strength training 3x10RM + no training</intervention_name>
    <description>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.</description>
    <arm_group_label>3x10RM + no training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Strength training 6x10RM + no training</intervention_name>
    <description>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.</description>
    <arm_group_label>6x10RM + no training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>3x10RM + 6x10RM</intervention_name>
    <description>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.</description>
    <arm_group_label>3x10RM + 6x10RM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Strength training more than 2 times per months for the last 6 months&#xD;
&#xD;
          -  Endurance training more than 3 hours per week&#xD;
&#xD;
          -  Adverse reactions to lidocaine&#xD;
&#xD;
          -  Consumption of supplements or medication affecting muscular adaptations to strength&#xD;
             training&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Inland Norway University of Applied Sciences</name>
      <address>
        <city>Lillehammer</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>May 18, 2020</last_update_submitted>
  <last_update_submitted_qc>May 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Contralateral</keyword>
  <keyword>Strength training</keyword>
  <keyword>Muscle</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified data will be made available to the academic community through the general biobank &quot;The Trainsome - effects of exercise and environment on human cells&quot; (REK-2013/2045, Regional Comitees for Medical and Health Research Ethics South East). Data will be available on request and will be restricted to scientists and/or projects with a sound scientific purpose and rationale.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03795025
org study id: Trainome 2019#014
nct id: NCT03795025
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Muscle fiber area
time frame: Changes over the course of the intervention (0-10 weeks)
description: Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry
measure: Body mass composition
time frame: Changes over the course of the intervention (0-10 weeks)
description: Body mass composition measured using Dual-energy X-ray absorptiometry (DXA)
measure: Rate of muscle protein synthesis (%/day)
time frame: Mesured over 3 days in week 7 of the study
description: 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.
measure: M. vastus lateralis thickness
time frame: Changes over the course of the intervention (0-10 weeks)
description: M. vastus lateralis thickness mesured by ultrasound
measure: Unilateral leg press strength (1RM test)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the lower body to exert maximal force during dynamic movements in a leg press
measure: Unilateral knee extension strength (1RM test)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the lower body to exert maximal force during dynamic movements in a knee extension
measure: Barbell bench press muscle strength (1RM test)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the upper body to exert maximal force during dynamic movements in a bench press
measure: Lying rowing muscle strength (1RM test)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the upper body to exert maximal force during dynamic movements in a lying row exercise
measure: Unilateral lower body isokinetic muscle strength at 60 and 240 deg per second in a mechanical dynamometer (Humac NORM)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the lower body to exert maximal force during isokinetic movements
measure: Unilateral lower body isometric muscle strength in a mechanical dynamometer (Humac NORM)
time frame: Changes over the course of the intervention (0-10 weeks)
description: The ability of muscles of the lower body to exert maximal force during isometric contractions
measure: One-legged cycling
time frame: Changes over the course of the intervention (0-10 weeks)
description: Performance indicies measured during an incremental one-legged cycling test
measure: Muscle phenotype
time frame: Changes over the course of the intervention (0-10 weeks)
description: Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry
measure: Muscle cell biological traits
time frame: Changes over the course of the intervention (0-10 weeks)
description: Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry
measure: Gene expression in skeletal muscle
time frame: Changes over the course of the intervention (0-10 weeks)
description: 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
measure: Protein abundances in skeletal muscle measured by western blot
time frame: Changes over the course of the intervention (0-10 weeks)
description: 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
measure: Hormones in blood
time frame: Changes over the course of the intervention (0-10 weeks)
description: Levels of hormones in blood
arm group label: 3x10RM + no training
arm group type: Experimental
arm group label: 6x10RM + no training
arm group type: Experimental
arm group label: 3x10RM + 6x10RM
arm group type: Experimental
arm group label: Control
arm group type: No Intervention
description: 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.
intervention type: Other
intervention name: Strength training 3x10RM + no training
description: 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.
arm group label: 3x10RM + no training
intervention type: Other
intervention name: Strength training 6x10RM + no training
description: 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.
arm group label: 6x10RM + no training
intervention type: Other
intervention name: 3x10RM + 6x10RM
description: 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.
arm group label: 3x10RM + 6x10RM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Norway
responsible party type: Sponsor
sharing ipd: Yes
ipd description: De-identified data will be made available to the academic community through the general biobank "The Trainsome - effects of exercise and environment on human cells" (REK-2013/2045, Regional Comitees for Medical and Health Research Ethics South East). Data will be available on request and will be restricted to scientists and/or projects with a sound scientific purpose and rationale.