<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/NCT02998892</url>
  </required_header>
  <id_info>
    <org_study_id>16-1769</org_study_id>
    <nct_id>NCT02998892</nct_id>
  </id_info>
  <brief_title>Effects of Microbouts of Activity on Metabolic Health</brief_title>
  <official_title>Effects of Microbouts of Activity on Metabolic Health</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</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>
      Population studies suggest that time spent in sedentary behaviors is associated with&#xD;
      all-cause mortality including obesity, diabetes, and cardiovascular diseases, independent of&#xD;
      time spent in exercise. Frequent interruptions to sedentary time are however beneficially&#xD;
      associated with metabolic health outcomes, even in individuals who exercise regularly. The&#xD;
      goal is to use integrative approach to understand the biological mechanisms that underlie&#xD;
      these associations in a longitudinal intervention study in overweight sedentary adults. The&#xD;
      investigators believe that the proposed study will provide an initial evidence base for the&#xD;
      health benefits of breaking up prolonged sitting with short bursts of activity. This&#xD;
      innovative strategy may be more effective at combating the adverse effects of sedentary&#xD;
      behaviors than more traditional approaches.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To compare the effects of 4-weeks of microbursts of moderate-intensity activity to a&#xD;
      calorically equivalent single bout of 45 minutes of moderate-intensity exercise training,&#xD;
      both performed 5 days per week for a total of 45 minutes, in free-living sedentary overweight&#xD;
      adults on:&#xD;
&#xD;
      Aim 1: plasma inflammatory and cardiometabolic health biomarkers in association with total&#xD;
      energy expenditure and time spent in sedentary behaviors.&#xD;
&#xD;
      H1: Microbursts of activity will result in higher daily energy expenditure and lower time&#xD;
      spent sedentary, as respectively measured with doubly labeled water and accelerometry, than&#xD;
      traditional exercise training. This will be associated with healthier inflammatory&#xD;
      Interleukin 1 alpha (IL1a), Interleukin 6 (IL6), Interleukin 10 (IL10), Tumour Necrosis&#xD;
      Factor alpha (TNFa) and cardiometabolic (triglycerides, cholesterol, C-Reactive Protein&#xD;
      (CRP), High-density lipoprotein (HDL), and Low-density lipoprotein (LDL) profiles compared to&#xD;
      those obtained with traditional exercise training program.&#xD;
&#xD;
      Aim 2: 24-hr total fat and carbohydrate oxidation, exogenous carbohydrate oxidation, dietary&#xD;
      fat trafficking between oxidation and incorporation into muscle lipid fractions, and&#xD;
      mitochondrial function.&#xD;
&#xD;
      H2: Both one single continuous bout and microbouts of activity will increase 24-hr total&#xD;
      (whole-room calorimetry) and dietary (D9-palmitate) fat oxidation due to greater&#xD;
      mitochondrial lipid oxidation (high resolution respirometry) and lower incorporation of&#xD;
      dietary fatty acid into muscle lipid fractions (D9-palmitate), as compared to baseline&#xD;
      sedentary control condition. Microbouts of activity will further result in greater increases&#xD;
      in 24-hr total (whole-room calorimetry) and exogenous (U-13C6 glucose) carbohydrate oxidation&#xD;
      and in mitochondrial carbohydrate-linked oxidation, than traditional isocaloric exercise&#xD;
      training.&#xD;
&#xD;
      Aim 3: Whole-body insulin sensitivity. H3: Both one single continuous bout and microbouts of&#xD;
      activity will improve whole-body insulin sensitivity Intravenous Glucose Tolerance Test&#xD;
      (IVGTT) compared to the baseline sedentary condition, but the improvement will likely be&#xD;
      higher with the microbouts of activity.&#xD;
&#xD;
      Exploratory aim: Self-perceived appetite, hunger, and levels of mood, fatigue and&#xD;
      vigor/energy.&#xD;
&#xD;
      H3: Microbursts of activity will result in less appetite, hunger and fatigue but in greater&#xD;
      feelings of vigor and overall well-being than traditional isocaloric exercise training. As a&#xD;
      result adherence to microbursts will be better than adherence to single bouts of physical&#xD;
      activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 9, 2017</start_date>
  <completion_date type="Actual">October 8, 2021</completion_date>
  <primary_completion_date type="Actual">October 8, 2021</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>Changes in sedentary time as measured by ActiPAL</measure>
    <time_frame>weeks 1-2 and weeks 5-6</time_frame>
    <description>Over each 2 week period, participants will be instructed to wear an ActiPAL (PALTechnologies: Glasgow, Scotland) activity monitor on their right leg. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities. The time-stamped &quot;event&quot; data file from the activPAL software will be used to determine time spent sitting/lying, standing and stepping per day.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in total substrate oxidation</measure>
    <time_frame>week 2 and week 7</time_frame>
    <description>Total fat oxidation during the test day will be determined using whole-room indirect calorimetry. O2 consumption and CO2 production will be determined from the flow rates and differences in gas concentrations between air entering and air exiting the calorimeter as previously described</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in insulin sensitivity</measure>
    <time_frame>week 2 and week 7</time_frame>
    <description>Insulin sensitivity will be determined via an insulin modified frequently sampled intra-venous glucose tolerance test (IVGTT). After baseline samples, intravenous glucose (0.3 g/kg) will be infused over 1 minute, followed by insulin at 0.03 U/kg, 20 minutes after glucose administration. Blood samples will be frequently sampled over 5 hours, and insulin sensitivity will be calculated using the Bergman minimal model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in total energy expenditure (TEE)</measure>
    <time_frame>week 1-2 and week 5-6</time_frame>
    <description>Total energy expenditure (TEE) will be measured before and at the end of the intervention using doubly labeled water (DLW) over a 10-day period, as previously described (31). Subjects will ingest premixed 2g/kg total body water (TBW), estimated as 73% of fat free mass) dose of DLW composed of 0.2 and 0.15 g/kg estimated TBW of H218O and 2H2O, respectively. Urine samples will be collected in duplicate on days 0, 6, 8 and 10. 2H and 18O enrichment will be determined in urine samples by isotope ratio mass spectrometry (Delta V Advantage IRMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Moderate-to-vigorous physical activity as measured by ActiGraph</measure>
    <time_frame>weeks 1-6</time_frame>
    <description>Over the same 10-day period, participants will be instructed to wear an Actigraph GT3X+ accelerometer (Actigraph, LLC, Fort Walton Beach, FL) on their hip. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma CRP concentration</measure>
    <time_frame>Once weekly for 5 weeks</time_frame>
    <description>Weekly fasting blood samples will be obtained for the measurements of CRP (mg/dL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Dietary Carbohydrate Oxidation</measure>
    <time_frame>week 2 and week 7</time_frame>
    <description>After the investigators have shown the subjects the procedure, subjects will collect their own hourly breath sampling for CO2 by blowing through a straw into two 15ml Vacutainers. Breath CO2 will be sampled directly from the Vacutainer with a syringe, and 13CO2 /12CO2 measured with IRMS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Dietary Fat Oxidation</measure>
    <time_frame>week 2 and week 7</time_frame>
    <description>Hourly urine sampling will be collected by the subjects for 24 hours and stored in 5mL cryovials at -20C until further analysis. To measure 2 hour fat oxidation, 2 hour/1 hour ratios from urine samples will be analyzed, as above described for the doubly labeled water method. The oxidation rate of glucose/water will be calculated from the cumulative recovery of 2 hours in total body water (TBW) as detailed previously.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mitochondria function</measure>
    <time_frame>week 2 and week 7</time_frame>
    <description>Freshly isolated skeletal muscle biopsies will be cut into small samples, the fibre bundles separated mechanically and partially teased apart and permeabilised. Small samples (2-5mg) will be added to the 2ml chamber of an Oroboros high-resolution respirometer with a mitochondrial respiration buffer. With the addition of several substrates, different states will be reached to analyse mitochondrial function. Pyruvate, malate and glutamate will be added as substrates to examine respiration through Complex I, succinate will be used to examine respiration through Complex II and octanoylcarnitine will be used to examine respiration through the electron-transferring flavoprotein, ETF.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Health Behavior</condition>
  <arm_group>
    <arm_group_label>Traditional Exercise Training</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 4 weeks. This intervention corresponds to the current recommendations.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Daily Microbursts of Activity</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 10 hours, 5 days/week, by brisk walking for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Traditional Exercise Training</intervention_name>
    <description>Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 4 weeks. This intervention corresponds to the current recommendations.</description>
    <arm_group_label>Traditional Exercise Training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Daily Microbursts of Activity</intervention_name>
    <description>Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 10 hours, 5 days/week, by brisk walking for 4 weeks.</description>
    <arm_group_label>Daily Microbursts of Activity</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Overweight but weight stable (+/- 3kg over previous 6 months) sedentary male and&#xD;
             female adults (n=30) will be recruited.&#xD;
&#xD;
          -  Ages between 18-45 years old&#xD;
&#xD;
          -  BMI of 25-35 kg/m2&#xD;
&#xD;
          -  Sedentary (&lt; 1hr/wk of moderate-to-vigorous activity, less than 6,500 steps per day as&#xD;
             measured for 5 days in free-living conditions with a pedometer). Based on subjects&#xD;
             self-report during the H&amp;P visit&#xD;
&#xD;
          -  The use of birth pill control will be accepted&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Any history of renal (present or past kidney failure, kidney transplant, dialysis or&#xD;
             kidney cysts),&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Cardiovascular (present or past atherosclerosis, heart attack, ischemic stroke, heart&#xD;
             failure)&#xD;
&#xD;
          -  Hepatic diseases (past or present hepatitis B or C, fibrosis, cirrhosis, NAFLD/NASH)&#xD;
&#xD;
          -  Type 1 or 2 diabetes&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Consumption of drugs (marijuana included)&#xD;
&#xD;
          -  Consumption of alcohol (&gt;40g/d)&#xD;
&#xD;
          -  HIV positivity&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  Any medications known to interfere with lipid or energy metabolism&#xD;
&#xD;
          -  Known physical activity contraindications&#xD;
&#xD;
          -  Major illness/physical problems (acute or chronic) that may limit their ability to&#xD;
             perform the walking activities&#xD;
&#xD;
          -  The blood draw will be used to objectively exclude peri- or postmenopausal women&#xD;
             (FSH&gt;25 mlU/mL in early follicular phase)&#xD;
&#xD;
          -  Hypertriglyceridemia (triglycerides &gt; 400mg/dL).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Audrey Bergouignan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>April 28, 2022</last_update_submitted>
  <last_update_submitted_qc>April 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sedentary Behavior</keyword>
  <patient_data>
    <sharing_ipd>No</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/NCT02998892
org study id: 16-1769
nct id: NCT02998892
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Population studies suggest that time spent in sedentary behaviors is associated with
      all-cause mortality including obesity, diabetes, and cardiovascular diseases, independent of
      time spent in exercise. Frequent interruptions to sedentary time are however beneficially
      associated with metabolic health outcomes, even in individuals who exercise regularly. The
      goal is to use integrative approach to understand the biological mechanisms that underlie
      these associations in a longitudinal intervention study in overweight sedentary adults. The
      investigators believe that the proposed study will provide an initial evidence base for the
      health benefits of breaking up prolonged sitting with short bursts of activity. This
      innovative strategy may be more effective at combating the adverse effects of sedentary
      behaviors than more traditional approaches.
To compare the effects of 4-weeks of microbursts of moderate-intensity activity to a
      calorically equivalent single bout of 45 minutes of moderate-intensity exercise training,
      both performed 5 days per week for a total of 45 minutes, in free-living sedentary overweight
      adults on:

      Aim 1: plasma inflammatory and cardiometabolic health biomarkers in association with total
      energy expenditure and time spent in sedentary behaviors.

      H1: Microbursts of activity will result in higher daily energy expenditure and lower time
      spent sedentary, as respectively measured with doubly labeled water and accelerometry, than
      traditional exercise training. This will be associated with healthier inflammatory
      Interleukin 1 alpha (IL1a), Interleukin 6 (IL6), Interleukin 10 (IL10), Tumour Necrosis
      Factor alpha (TNFa) and cardiometabolic (triglycerides, cholesterol, C-Reactive Protein
      (CRP), High-density lipoprotein (HDL), and Low-density lipoprotein (LDL) profiles compared to
      those obtained with traditional exercise training program.

      Aim 2: 24-hr total fat and carbohydrate oxidation, exogenous carbohydrate oxidation, dietary
      fat trafficking between oxidation and incorporation into muscle lipid fractions, and
      mitochondrial function.

      H2: Both one single continuous bout and microbouts of activity will increase 24-hr total
      (whole-room calorimetry) and dietary (D9-palmitate) fat oxidation due to greater
      mitochondrial lipid oxidation (high resolution respirometry) and lower incorporation of
      dietary fatty acid into muscle lipid fractions (D9-palmitate), as compared to baseline
      sedentary control condition. Microbouts of activity will further result in greater increases
      in 24-hr total (whole-room calorimetry) and exogenous (U-13C6 glucose) carbohydrate oxidation
      and in mitochondrial carbohydrate-linked oxidation, than traditional isocaloric exercise
      training.

      Aim 3: Whole-body insulin sensitivity. H3: Both one single continuous bout and microbouts of
      activity will improve whole-body insulin sensitivity Intravenous Glucose Tolerance Test
      (IVGTT) compared to the baseline sedentary condition, but the improvement will likely be
      higher with the microbouts of activity.

      Exploratory aim: Self-perceived appetite, hunger, and levels of mood, fatigue and
      vigor/energy.

      H3: Microbursts of activity will result in less appetite, hunger and fatigue but in greater
      feelings of vigor and overall well-being than traditional isocaloric exercise training. As a
      result adherence to microbursts will be better than adherence to single bouts of physical
      activity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Changes in sedentary time as measured by ActiPAL
time frame: weeks 1-2 and weeks 5-6
description: Over each 2 week period, participants will be instructed to wear an ActiPAL (PALTechnologies: Glasgow, Scotland) activity monitor on their right leg. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities. The time-stamped "event" data file from the activPAL software will be used to determine time spent sitting/lying, standing and stepping per day.
measure: Changes in total substrate oxidation
time frame: week 2 and week 7
description: Total fat oxidation during the test day will be determined using whole-room indirect calorimetry. O2 consumption and CO2 production will be determined from the flow rates and differences in gas concentrations between air entering and air exiting the calorimeter as previously described
measure: Changes in insulin sensitivity
time frame: week 2 and week 7
description: Insulin sensitivity will be determined via an insulin modified frequently sampled intra-venous glucose tolerance test (IVGTT). After baseline samples, intravenous glucose (0.3 g/kg) will be infused over 1 minute, followed by insulin at 0.03 U/kg, 20 minutes after glucose administration. Blood samples will be frequently sampled over 5 hours, and insulin sensitivity will be calculated using the Bergman minimal model.
measure: Changes in total energy expenditure (TEE)
time frame: week 1-2 and week 5-6
description: Total energy expenditure (TEE) will be measured before and at the end of the intervention using doubly labeled water (DLW) over a 10-day period, as previously described (31). Subjects will ingest premixed 2g/kg total body water (TBW), estimated as 73% of fat free mass) dose of DLW composed of 0.2 and 0.15 g/kg estimated TBW of H218O and 2H2O, respectively. Urine samples will be collected in duplicate on days 0, 6, 8 and 10. 2H and 18O enrichment will be determined in urine samples by isotope ratio mass spectrometry (Delta V Advantage IRMS)
measure: Changes in Moderate-to-vigorous physical activity as measured by ActiGraph
time frame: weeks 1-6
description: Over the same 10-day period, participants will be instructed to wear an Actigraph GT3X+ accelerometer (Actigraph, LLC, Fort Walton Beach, FL) on their hip. Participants will be instructed to wear the monitors at all times except when sleeping or participating in water-based activities.
measure: Changes in plasma CRP concentration
time frame: Once weekly for 5 weeks
description: Weekly fasting blood samples will be obtained for the measurements of CRP (mg/dL).
measure: Changes in Dietary Carbohydrate Oxidation
time frame: week 2 and week 7
description: After the investigators have shown the subjects the procedure, subjects will collect their own hourly breath sampling for CO2 by blowing through a straw into two 15ml Vacutainers. Breath CO2 will be sampled directly from the Vacutainer with a syringe, and 13CO2 /12CO2 measured with IRMS.
measure: Changes in Dietary Fat Oxidation
time frame: week 2 and week 7
description: Hourly urine sampling will be collected by the subjects for 24 hours and stored in 5mL cryovials at -20C until further analysis. To measure 2 hour fat oxidation, 2 hour/1 hour ratios from urine samples will be analyzed, as above described for the doubly labeled water method. The oxidation rate of glucose/water will be calculated from the cumulative recovery of 2 hours in total body water (TBW) as detailed previously.
measure: Changes in Mitochondria function
time frame: week 2 and week 7
description: Freshly isolated skeletal muscle biopsies will be cut into small samples, the fibre bundles separated mechanically and partially teased apart and permeabilised. Small samples (2-5mg) will be added to the 2ml chamber of an Oroboros high-resolution respirometer with a mitochondrial respiration buffer. With the addition of several substrates, different states will be reached to analyse mitochondrial function. Pyruvate, malate and glutamate will be added as substrates to examine respiration through Complex I, succinate will be used to examine respiration through Complex II and octanoylcarnitine will be used to examine respiration through the electron-transferring flavoprotein, ETF.
arm group label: Traditional Exercise Training
arm group type: Active Comparator
description: Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 4 weeks. This intervention corresponds to the current recommendations.
arm group label: Daily Microbursts of Activity
arm group type: Experimental
description: Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 10 hours, 5 days/week, by brisk walking for 4 weeks.
intervention type: Behavioral
intervention name: Traditional Exercise Training
description: Participants will be asked to perform moderate-intensity exercise (brisk walking) for 45 minutes for 5 days/week for 4 weeks. This intervention corresponds to the current recommendations.
arm group label: Traditional Exercise Training
intervention type: Behavioral
intervention name: Daily Microbursts of Activity
description: Participants will be asked to break up their sedentary activities of daily living for 5-minutes every hour for 10 hours, 5 days/week, by brisk walking for 4 weeks.
arm group label: Daily Microbursts of Activity
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Audrey Bergouignan, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No