<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/NCT02982408</url>
  </required_header>
  <id_info>
    <org_study_id>H-4-2014-128</org_study_id>
    <nct_id>NCT02982408</nct_id>
  </id_info>
  <brief_title>Impact of Overfeeding and Following Exercise Training in Individuals With and Without Increased Risk of Type 2 Diabetes</brief_title>
  <official_title>Can Exercise Training Revert and/or Minimize the Deleterious Cardiometabolic Effects of Carbohydrate Overfeeding in Individuals With and Without Increased Risk of Type 2 Diabetes?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Augustinus Fonden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Low birth weight (LBW), a marker of impaired fetal growth is an independent and strong risk&#xD;
      factor for type 2 diabetes (T2D). A western lifestyle characterized by a surplus of calories,&#xD;
      and/or a low physical activity level, associated with increased fat storage and altered lipid&#xD;
      metabolism plays a central role in the pathogenesis of insulin resistance and T2D. Using&#xD;
      state-of-the-art large-scale integrative physiology studies combined with basic studies of&#xD;
      adipose and muscle tissue stem cell functions, the investigators aim to determine if LBW&#xD;
      individuals exhibit decreased subcutaneous adipose tissue expandability, postprandial&#xD;
      hyperlipidaemia and ectopic fat accumulation when exposed to 4 weeks of carbohydrate&#xD;
      overfeeding. The investigators will subsequently examine if exercise training can revert&#xD;
      and/or minimize the deleterious effects of carbohydrate overfeeding in a possibly birth&#xD;
      weight differential manner.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">March 2019</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adipose tissue expandability</measure>
    <time_frame>baseline</time_frame>
    <description>Percent (%) subcutaneous, visceral adipose tissue and hepatic fat will be determined by MR scanning in the two groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adipose tissue expandability</measure>
    <time_frame>Difference between the two groups at baseline, after 4 weeks overfeeding and after 12 weeks exercise training.</time_frame>
    <description>Percent (%) subcutaneous, visceral adipose tissue and hepatic fat will be determined by MR scanning in the two groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucose turnover rate</measure>
    <time_frame>Baseline, 4 weeks overfeeding, 12 weeks training</time_frame>
    <description>Turnover rates will be measured after a 5 hr mealtest by use isotopic tracers in the two groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid turnover rate</measure>
    <time_frame>Baseline, 4 weeks overfeeding, 12 weeks training</time_frame>
    <description>Turnover rates will be measured after a 5 hr mealtest by use isotopic tracers in the two groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epigenetics</measure>
    <time_frame>Baseline, 4 weeks overfeeding, 12 weeks training</time_frame>
    <description>Marks of adipose tissue, skeletal muscle stem cell and differentiated cell type genomes.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <condition>Insulin Resistance</condition>
  <condition>Dyslipidemia</condition>
  <arm_group>
    <arm_group_label>Low birth weight (LBW)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 males born at term (weeks 39-41) in 1979-1981 with LBW (BW&lt;10th percentile)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal birth weight (NBW)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 BMI- and age-matched males born at term (weeks 39-41) with normal birth weight (NBW) control individuals (BW: 50-90th percentile)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>High carbohydrate overfeeding</intervention_name>
    <description>All participant's individual energy requirement will be determined in mega joules (MJ) per day. The energy requirement will be multiplied by a factor 1.5 for a low physical activity level (PAL). The MJ will be rounded up or down to the nearest whole number.&#xD;
The participant will receive food corresponding to ~25% additional energy above their calculated energy requirement. The 25% extra energy will be supplied to the participants for 4 weeks in the form of food containing simple carbohydrates. The subjects will be given a daily snack package containing processed foods or refined foods such as sweets, cookies, soft drinks, juice etc. To ensure an adequate energy surplus (i.e. weight gain), physical activity has to be decreased to a low level during the 4 weeks overfeeding period.</description>
    <arm_group_label>Low birth weight (LBW)</arm_group_label>
    <arm_group_label>Normal birth weight (NBW)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Half of the participants will be randomized to a 3-month exercise-training program.&#xD;
The training program consists of combined aerobic training and strength training. The training program is performed unsupervised 3 times per week 45 minutes per session for 3 months in the local fitness center. Before engaging in the training program a maximal oxygen consumption test (VO2 max) are conducted and the maximal heartrate (HR) are determined.Participants are wearing the Polar V800 HR monitor and are asked to note their HR in a training log at the end of the last interval at each training session. The strength training program consist of 6 exercises (2 exercises paired together) involving the large muscle groups. The first training session is completed supervised at Rigshospitalet . After 6 weeks the training program is adjusted. Compliance will be ensured by phone calls, text messages and e-mails from study personnel.</description>
    <arm_group_label>Low birth weight (LBW)</arm_group_label>
    <arm_group_label>Normal birth weight (NBW)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Normal physical activity</intervention_name>
    <description>The other half of the participants will be randomized to a 3-month with normal physical activity level (control).&#xD;
The participants will have to return to the physical activity level they had before entering the study (baseline level). Compliance will be ensured by phone calls and text messages from study personnel. The subjects will wear a simple pedometer on the hip showing the number of steps. Once a week a text message (SMS-track) is automatically sent asking the participants to enter the weekly number of steps. The test personnel receive the reply and contact the participant if the number of steps does not match the baseline level. During the first and the last 7 days of the exercise intervention participants are wearing 2 accelerometers measuring their physical activity behavior.</description>
    <arm_group_label>Low birth weight (LBW)</arm_group_label>
    <arm_group_label>Normal birth weight (NBW)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  without known disease (approved health examination)&#xD;
&#xD;
          -  caucasian&#xD;
&#xD;
          -  born at term (weeks 39-41) in Denmark&#xD;
&#xD;
          -  recruited from the national Danish Birth Registry&#xD;
&#xD;
          -  born with either low or normal birthweight (see previous)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  family history of diabetes in two generations (1st and 2nd degree relatives)&#xD;
&#xD;
          -  self-reported high physical activity level (&gt;10hrs /week).&#xD;
&#xD;
          -  weight loss/gain &gt;3 kg within the past 6 months&#xD;
&#xD;
          -  alcohol intake of more than general recommendations&#xD;
&#xD;
          -  substance abuser&#xD;
&#xD;
          -  intake of medication know to affect outcomes&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charlotte Brøns, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Allan Vaag, PhD, DMsc</last_name>
    <role>Study Director</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalet, Denmark</name>
      <address>
        <city>Copenhagen</city>
        <state>Capital Region</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>September 3, 2019</last_update_submitted>
  <last_update_submitted_qc>September 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Charlotte Brøns</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <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>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <!-- 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/NCT02982408
org study id: H-4-2014-128
nct id: NCT02982408
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Low birth weight (LBW), a marker of impaired fetal growth is an independent and strong risk
      factor for type 2 diabetes (T2D). A western lifestyle characterized by a surplus of calories,
      and/or a low physical activity level, associated with increased fat storage and altered lipid
      metabolism plays a central role in the pathogenesis of insulin resistance and T2D. Using
      state-of-the-art large-scale integrative physiology studies combined with basic studies of
      adipose and muscle tissue stem cell functions, the investigators aim to determine if LBW
      individuals exhibit decreased subcutaneous adipose tissue expandability, postprandial
      hyperlipidaemia and ectopic fat accumulation when exposed to 4 weeks of carbohydrate
      overfeeding. The investigators will subsequently examine if exercise training can revert
      and/or minimize the deleterious effects of carbohydrate overfeeding in a possibly birth
      weight differential manner.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Adipose tissue expandability
time frame: baseline
description: Percent (%) subcutaneous, visceral adipose tissue and hepatic fat will be determined by MR scanning in the two groups
measure: Adipose tissue expandability
time frame: Difference between the two groups at baseline, after 4 weeks overfeeding and after 12 weeks exercise training.
description: Percent (%) subcutaneous, visceral adipose tissue and hepatic fat will be determined by MR scanning in the two groups
measure: Glucose turnover rate
time frame: Baseline, 4 weeks overfeeding, 12 weeks training
description: Turnover rates will be measured after a 5 hr mealtest by use isotopic tracers in the two groups
measure: Lipid turnover rate
time frame: Baseline, 4 weeks overfeeding, 12 weeks training
description: Turnover rates will be measured after a 5 hr mealtest by use isotopic tracers in the two groups
measure: Epigenetics
time frame: Baseline, 4 weeks overfeeding, 12 weeks training
description: Marks of adipose tissue, skeletal muscle stem cell and differentiated cell type genomes.
arm group label: Low birth weight (LBW)
arm group type: Experimental
description: 25 males born at term (weeks 39-41) in 1979-1981 with LBW (BW<10th percentile)
arm group label: Normal birth weight (NBW)
arm group type: Experimental
description: 25 BMI- and age-matched males born at term (weeks 39-41) with normal birth weight (NBW) control individuals (BW: 50-90th percentile)
intervention type: Dietary Supplement
intervention name: High carbohydrate overfeeding
description: All participant's individual energy requirement will be determined in mega joules (MJ) per day. The energy requirement will be multiplied by a factor 1.5 for a low physical activity level (PAL). The MJ will be rounded up or down to the nearest whole number.
The participant will receive food corresponding to ~25% additional energy above their calculated energy requirement. The 25% extra energy will be supplied to the participants for 4 weeks in the form of food containing simple carbohydrates. The subjects will be given a daily snack package containing processed foods or refined foods such as sweets, cookies, soft drinks, juice etc. To ensure an adequate energy surplus (i.e. weight gain), physical activity has to be decreased to a low level during the 4 weeks overfeeding period.
arm group label: Low birth weight (LBW)
arm group label: Normal birth weight (NBW)
intervention type: Behavioral
intervention name: Exercise
description: Half of the participants will be randomized to a 3-month exercise-training program.
The training program consists of combined aerobic training and strength training. The training program is performed unsupervised 3 times per week 45 minutes per session for 3 months in the local fitness center. Before engaging in the training program a maximal oxygen consumption test (VO2 max) are conducted and the maximal heartrate (HR) are determined.Participants are wearing the Polar V800 HR monitor and are asked to note their HR in a training log at the end of the last interval at each training session. The strength training program consist of 6 exercises (2 exercises paired together) involving the large muscle groups. The first training session is completed supervised at Rigshospitalet . After 6 weeks the training program is adjusted. Compliance will be ensured by phone calls, text messages and e-mails from study personnel.
arm group label: Low birth weight (LBW)
arm group label: Normal birth weight (NBW)
intervention type: Behavioral
intervention name: Normal physical activity
description: The other half of the participants will be randomized to a 3-month with normal physical activity level (control).
The participants will have to return to the physical activity level they had before entering the study (baseline level). Compliance will be ensured by phone calls and text messages from study personnel. The subjects will wear a simple pedometer on the hip showing the number of steps. Once a week a text message (SMS-track) is automatically sent asking the participants to enter the weekly number of steps. The test personnel receive the reply and contact the participant if the number of steps does not match the baseline level. During the first and the last 7 days of the exercise intervention participants are wearing 2 accelerometers measuring their physical activity behavior.
arm group label: Low birth weight (LBW)
arm group label: Normal birth weight (NBW)
criteria: 
gender: Male
minimum age: 35 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Charlotte Brøns, PhD
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
last name: Allan Vaag, PhD, DMsc
role: Study Director
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Charlotte Brøns
investigator title: PhD
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Dyslipidemias