<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/NCT03278704</url>
  </required_header>
  <id_info>
    <org_study_id>RG_16-218</org_study_id>
    <secondary_id>ERN_16-1612</secondary_id>
    <secondary_id>RRK6071</secondary_id>
    <nct_id>NCT03278704</nct_id>
  </id_info>
  <brief_title>Concurrent Training in Type 2 Diabetes</brief_title>
  <acronym>CONTRADIA</acronym>
  <official_title>Effects of Concurrent Resistance Exercise and High-intensity Interval Exercise Training on Skeletal Muscle Adaptations in Individuals With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Loughborough University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Metabolic Fitness Association, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Università degli studi di Roma Foro Italico</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Birmingham</source>
  <oversight_info>
    <has_dmc>No</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>
      It is recommended that individuals perform a combination of resistance exercise (RE) and&#xD;
      endurance exercise. Lack of time is often cited as a reason for being unable to meet current&#xD;
      exercise guidelines. Therefore, combining both forms in one session may be beneficial.&#xD;
      However, research continues to elucidate whether interference of adaptive outcomes occurs&#xD;
      when RE and endurance exercise are performed concurrently. A proposed interference effect&#xD;
      suggests that concurrent training may dampen RE-induced adaptations (e.g., muscle strength&#xD;
      and growth) compared to RE only.&#xD;
&#xD;
      The propose of this investigation is to determine the effects of concurrent RE and&#xD;
      high-intensity interval training (HIIT), compared to RE only, on muscle health and&#xD;
      cardiovascular risk in sedentary, middle-aged (40-65 years) who are overweight/obese with&#xD;
      type 2 diabetes mellitus (T2DM). The investigators will measure the effects on muscle&#xD;
      strength, muscle growth, cardiovascular fitness, glycaemic control and markers of&#xD;
      cardiovascular risk before and after an 8-week training program. Data will be obtained&#xD;
      through the analysis of skeletal muscle samples, blood samples, magnetic resonance imaging,&#xD;
      questionnaires and exercise performance tests.It is hypothesized that concurrent RE + HIIT&#xD;
      will amplify the exercise-induced muscle growth response, which will result in greater&#xD;
      satellite cell content, compared to RE alone. As a result, this will lead to greater skeletal&#xD;
      muscle mass and strength after RE + HIIT compared to RE in isolation.&#xD;
&#xD;
      A finding that concurrent resistance training and HIIT does not impede muscle adaptations&#xD;
      could offer future strategies to minimize exercise time commitment whilst still maximizing&#xD;
      the physiological benefits of both resistance and endurance exercise through a single&#xD;
      training session. This may therefore provide an effective exercise strategy in the prevention&#xD;
      and/or treatment of T2DM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data analysis will be performed using IBM SPSS statistical software (IBM Corp., Armonk, New&#xD;
      York, USA). All data will be checked for normality and appropriate log transformations&#xD;
      applied prior to analysis of variance (ANOVA) for primary and secondary outcomes. Satellite&#xD;
      cell content will be compared using a two-way, mixed-model ANOVA with one within (2 levels;&#xD;
      pre- and post-training) and one between factor (2 level; exercise group) with significance&#xD;
      set at P &lt; 0.05.&#xD;
&#xD;
      Based on a mixed ANOVA with between- and within-participant factors, and previously published&#xD;
      data (Babcock et al. 2012), a sample size of 24 participants (12 per group) will provide a&#xD;
      power of 84%. This sample size will allow detection of a mean change in satellite cell&#xD;
      content of 2.35, assuming standard deviations of the change from pre- to post-training as&#xD;
      2.266 and 1.331 in the two exercise groups. Sample size calculation was performed with an&#xD;
      alpha error of 0.05. SamplePower 2.0 (SPSS Inc., Chicago, Illinois, USA) software was used to&#xD;
      determine sample size.&#xD;
&#xD;
      This study will combine data collected at the University of Birmingham with previously&#xD;
      collected data from an identical study design performed by a co-investigator (Dr Pugh) in&#xD;
      Rome, Italy. The previous study has collected data from 10 participants across both exercise&#xD;
      groups (RE, N = 7; RE + HIIT, N = 3). Therefore, it is necessary for the present study to&#xD;
      recruit a further 14 participants (RE, N = 5, RE + HIIT, N = 9) in order to achieve a sample&#xD;
      size of 24 participants (12 per group). However, based on an assumption of a 25% drop-out&#xD;
      rate, the total minimal sample necessary will be 19 participants (RE, N = 7; RE + HIIT, N =&#xD;
      12).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Enrollment goal not met in allotted recruitment period&#xD;
  </why_stopped>
  <start_date type="Actual">December 6, 2017</start_date>
  <completion_date type="Actual">July 12, 2018</completion_date>
  <primary_completion_date type="Actual">July 12, 2018</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>
    <intervention_model_description>This is an exploratory randomized controlled trial. Participants will complete a parallel designed study, in which they will be randomly assigned to a resistance exercise (RE) only or concurrent RE and high-intensity interval training (RE + HIIT) group.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in fibre-type specific satellite cell content</measure>
    <time_frame>Prior to the 8-week training intervention and 72 hours after the last training session</time_frame>
    <description>Assessed using immunofluorescence microscopy (Pax7-positive cells)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in muscle-specific gene expression related to growth adaptations</measure>
    <time_frame>Prior to the 8-week training intervention and 72 hours after the last training session</time_frame>
    <description>Assessed using reverse-transcription polymerase chain reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in muscle fibre size</measure>
    <time_frame>Prior to the 8-week training intervention and 72 hours after the last training session</time_frame>
    <description>Assessed using immunofluorescence microscopy techniques to determine muscle fibre type-specific cross-sectional area</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in muscle size</measure>
    <time_frame>Prior to the 8-week training intervention and 48 hours after the last training session</time_frame>
    <description>Assessed using MRI to determine whole and individual muscle group cross-section area and total muscle volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in isometric muscle strength</measure>
    <time_frame>Prior to the 8-week training intervention and 6 days after the last training session</time_frame>
    <description>Assessed using a dynamometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in isokinetic muscle strength</measure>
    <time_frame>Prior to the 8-week training intervention and 6 days after the last training session</time_frame>
    <description>Assessed using a dynamometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiorespiratory fitness</measure>
    <time_frame>Prior to the 8-week training intervention and 6 days after the last training session</time_frame>
    <description>Assessed using a V̇O2 peak test on a cycle ergometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in habitual physical activity levels</measure>
    <time_frame>Prior to the 8-week training intervention and 1 week after the last training session</time_frame>
    <description>Assessed using 7-day continuous accelerometry data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in exercise enjoyment</measure>
    <time_frame>After the first and last training session</time_frame>
    <description>Assessed using validated questionnaires (PACES)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glycaemic control</measure>
    <time_frame>Prior to the 8-week training intervention and 72 hours after the last training session</time_frame>
    <description>Assessed using blood analysis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>RE training only</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>RE only - Progressive resistance exercise training only (leg extension, leg step up, chest press and pull down).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Concurrent RE + HIIT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RE + HIIT - Progressive resistance exercise training (leg extension, leg step up, chest press and pull down) followed by HIIT (10 x 1 min at 90% heart rate maximum).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>RE only</intervention_name>
    <description>8 weeks of supervised training. Three times weekly with no more than two non-consecutive days without exercise.</description>
    <arm_group_label>RE training only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>RE + HIIT</intervention_name>
    <description>8 weeks of supervised training. Three times weekly with no more than two non-consecutive days without exercise. Concurrent training: RE followed by HIIT within the same session.</description>
    <arm_group_label>Concurrent RE + HIIT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male sex&#xD;
&#xD;
          -  White British/European&#xD;
&#xD;
          -  Aged between 40 and 65 years at the time of screening&#xD;
&#xD;
          -  Have a body mass index (BMI; body weight/height in m2) between 27 and 40 kg/m2&#xD;
&#xD;
          -  Sedentary/untrained for at least 1 year (based on physical activity self-reports of&#xD;
             fewer than two sessions of structured exercise per week last &lt;30 min)&#xD;
&#xD;
          -  T2DM (American Diabetes Association 2014) for more than 1 year&#xD;
&#xD;
          -  Central obesity (defined as waist circumference ≥94 cm for males)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently involved in research or have recently (&lt;6 months) been involved in any&#xD;
             research prior to recruitment&#xD;
&#xD;
          -  Any condition limiting or contraindicating physical activity; including diabetic&#xD;
             peripheral neuropathy, and coronary or peripheral artery disease&#xD;
&#xD;
          -  Previous myocardial infarction, previous or current angina, shortness of breath, or&#xD;
             other symptoms suggestive of heart failure&#xD;
&#xD;
          -  Insulin medication&#xD;
&#xD;
          -  HbA1c more than 75 mmol/mol (9%)&#xD;
&#xD;
          -  Uncontrollable hypertension: systolic blood pressure ≥160 mmHg and diastolic blood&#xD;
             pressure ≥100 mmHg&#xD;
&#xD;
          -  Not weight stable for the last three months&#xD;
&#xD;
          -  Smokers (within the last 12 months)&#xD;
&#xD;
          -  Anticoagulant medication, such as warfarin or newer anticoagulant drugs. If&#xD;
             participants are on aspirin medication, this would need to be stopped for 3 days prior&#xD;
             to and during the day of any biopsy visit unless contraindicated (in which case&#xD;
             participants would be excluded).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Professor M Nimmo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.</citation>
    <PMID>24357209</PMID>
  </reference>
  <reference>
    <citation>Babcock L, Escano M, D'Lugos A, Todd K, Murach K, Luden N. Concurrent aerobic exercise interferes with the satellite cell response to acute resistance exercise. Am J Physiol Regul Integr Comp Physiol. 2012 Jun 15;302(12):R1458-65. doi: 10.1152/ajpregu.00035.2012. Epub 2012 Apr 4.</citation>
    <PMID>22492813</PMID>
  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>July 13, 2018</last_update_submitted>
  <last_update_submitted_qc>July 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Concurrent training</keyword>
  <keyword>Type 2 Diabetes Mellitus</keyword>
  <keyword>Resistance exercise</keyword>
  <keyword>High-Intensity Interval Training (HIIT)</keyword>
  <keyword>Muscle hypertrophy</keyword>
  <keyword>Interference effect</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03278704
org study id: RG_16-218
secondary id: ERN_16-1612
secondary id: RRK6071
nct id: NCT03278704
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is recommended that individuals perform a combination of resistance exercise (RE) and
      endurance exercise. Lack of time is often cited as a reason for being unable to meet current
      exercise guidelines. Therefore, combining both forms in one session may be beneficial.
      However, research continues to elucidate whether interference of adaptive outcomes occurs
      when RE and endurance exercise are performed concurrently. A proposed interference effect
      suggests that concurrent training may dampen RE-induced adaptations (e.g., muscle strength
      and growth) compared to RE only.

      The propose of this investigation is to determine the effects of concurrent RE and
      high-intensity interval training (HIIT), compared to RE only, on muscle health and
      cardiovascular risk in sedentary, middle-aged (40-65 years) who are overweight/obese with
      type 2 diabetes mellitus (T2DM). The investigators will measure the effects on muscle
      strength, muscle growth, cardiovascular fitness, glycaemic control and markers of
      cardiovascular risk before and after an 8-week training program. Data will be obtained
      through the analysis of skeletal muscle samples, blood samples, magnetic resonance imaging,
      questionnaires and exercise performance tests.It is hypothesized that concurrent RE + HIIT
      will amplify the exercise-induced muscle growth response, which will result in greater
      satellite cell content, compared to RE alone. As a result, this will lead to greater skeletal
      muscle mass and strength after RE + HIIT compared to RE in isolation.

      A finding that concurrent resistance training and HIIT does not impede muscle adaptations
      could offer future strategies to minimize exercise time commitment whilst still maximizing
      the physiological benefits of both resistance and endurance exercise through a single
      training session. This may therefore provide an effective exercise strategy in the prevention
      and/or treatment of T2DM.
Data analysis will be performed using IBM SPSS statistical software (IBM Corp., Armonk, New
      York, USA). All data will be checked for normality and appropriate log transformations
      applied prior to analysis of variance (ANOVA) for primary and secondary outcomes. Satellite
      cell content will be compared using a two-way, mixed-model ANOVA with one within (2 levels;
      pre- and post-training) and one between factor (2 level; exercise group) with significance
      set at P < 0.05.

      Based on a mixed ANOVA with between- and within-participant factors, and previously published
      data (Babcock et al. 2012), a sample size of 24 participants (12 per group) will provide a
      power of 84%. This sample size will allow detection of a mean change in satellite cell
      content of 2.35, assuming standard deviations of the change from pre- to post-training as
      2.266 and 1.331 in the two exercise groups. Sample size calculation was performed with an
      alpha error of 0.05. SamplePower 2.0 (SPSS Inc., Chicago, Illinois, USA) software was used to
      determine sample size.

      This study will combine data collected at the University of Birmingham with previously
      collected data from an identical study design performed by a co-investigator (Dr Pugh) in
      Rome, Italy. The previous study has collected data from 10 participants across both exercise
      groups (RE, N = 7; RE + HIIT, N = 3). Therefore, it is necessary for the present study to
      recruit a further 14 participants (RE, N = 5, RE + HIIT, N = 9) in order to achieve a sample
      size of 24 participants (12 per group). However, based on an assumption of a 25% drop-out
      rate, the total minimal sample necessary will be 19 participants (RE, N = 7; RE + HIIT, N =
      12).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an exploratory randomized controlled trial. Participants will complete a parallel designed study, in which they will be randomly assigned to a resistance exercise (RE) only or concurrent RE and high-intensity interval training (RE + HIIT) group.
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in fibre-type specific satellite cell content
time frame: Prior to the 8-week training intervention and 72 hours after the last training session
description: Assessed using immunofluorescence microscopy (Pax7-positive cells)
measure: Change in muscle-specific gene expression related to growth adaptations
time frame: Prior to the 8-week training intervention and 72 hours after the last training session
description: Assessed using reverse-transcription polymerase chain reactions
measure: Change in muscle fibre size
time frame: Prior to the 8-week training intervention and 72 hours after the last training session
description: Assessed using immunofluorescence microscopy techniques to determine muscle fibre type-specific cross-sectional area
measure: Change in muscle size
time frame: Prior to the 8-week training intervention and 48 hours after the last training session
description: Assessed using MRI to determine whole and individual muscle group cross-section area and total muscle volume
measure: Change in isometric muscle strength
time frame: Prior to the 8-week training intervention and 6 days after the last training session
description: Assessed using a dynamometer
measure: Change in isokinetic muscle strength
time frame: Prior to the 8-week training intervention and 6 days after the last training session
description: Assessed using a dynamometer
measure: Change in cardiorespiratory fitness
time frame: Prior to the 8-week training intervention and 6 days after the last training session
description: Assessed using a V̇O2 peak test on a cycle ergometer
measure: Change in habitual physical activity levels
time frame: Prior to the 8-week training intervention and 1 week after the last training session
description: Assessed using 7-day continuous accelerometry data
measure: Change in exercise enjoyment
time frame: After the first and last training session
description: Assessed using validated questionnaires (PACES)
measure: Change in glycaemic control
time frame: Prior to the 8-week training intervention and 72 hours after the last training session
description: Assessed using blood analysis
arm group label: RE training only
arm group type: Other
description: RE only - Progressive resistance exercise training only (leg extension, leg step up, chest press and pull down).
arm group label: Concurrent RE + HIIT
arm group type: Experimental
description: RE + HIIT - Progressive resistance exercise training (leg extension, leg step up, chest press and pull down) followed by HIIT (10 x 1 min at 90% heart rate maximum).
intervention type: Other
intervention name: RE only
description: 8 weeks of supervised training. Three times weekly with no more than two non-consecutive days without exercise.
arm group label: RE training only
intervention type: Other
intervention name: RE + HIIT
description: 8 weeks of supervised training. Three times weekly with no more than two non-consecutive days without exercise. Concurrent training: RE followed by HIIT within the same session.
arm group label: Concurrent RE + HIIT
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Professor M Nimmo, PhD
role: Principal Investigator
affiliation: University of Birmingham
facility: 
country: United Kingdom
citation: American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.
PMID: 24357209
citation: Babcock L, Escano M, D'Lugos A, Todd K, Murach K, Luden N. Concurrent aerobic exercise interferes with the satellite cell response to acute resistance exercise. Am J Physiol Regul Integr Comp Physiol. 2012 Jun 15;302(12):R1458-65. doi: 10.1152/ajpregu.00035.2012. Epub 2012 Apr 4.
PMID: 22492813
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: Undecided