<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/NCT03284216</url>
  </required_header>
  <id_info>
    <org_study_id>ERN_16-0193</org_study_id>
    <nct_id>NCT03284216</nct_id>
  </id_info>
  <brief_title>Hyperglycemia and Exercise.</brief_title>
  <acronym>GlucotoxEx</acronym>
  <official_title>The Effects of Hyperglycemia on the Response to Acute Exercise.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      This study will determine whether exposure to short-term high blood glucose levels impairs&#xD;
      exercise-induced adaptations in glucose tolerance, and whether the pattern of high blood&#xD;
      glucose levels plays a role.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Healthy male volunteers will undergo a screening visit and four experimental trials.&#xD;
&#xD;
      Screening Visit: Having read the participant info sheet, a study investigator will discuss&#xD;
      the project with the potential participant who will have the chance to ask any questions.&#xD;
      Informed consent will be sought and a General Health Questionnaire will be completed. Body&#xD;
      weight, height, and skinfold measurements will be taken. Participants will also complete an&#xD;
      exercise test to measure V̇O2max test along with heart rate and blood pressure measurements.&#xD;
&#xD;
      Individuals eligible for inclusion in the study will then return to the lab for four&#xD;
      experimental trials, each separated by ~1 week. Trials will be completed using a randomised,&#xD;
      counter-balanced, cross-over design. Between experimental trials, participants will be&#xD;
      instructed to maintain their normal diet and activity habits. During the 48 hours prior to&#xD;
      each experimental trial participants will be instructed to refrain from vigorous exercise and&#xD;
      alcohol. For 3 days prior to each experimental trial, participants will record their dietary&#xD;
      intake, and wear an accelerometer and a continuous glucose monitor to measure physical&#xD;
      activity levels and glucose control.&#xD;
&#xD;
      Experimental Trials: Participants will arrive at the laboratory in the morning (~8 am)&#xD;
      following an overnight (~10 hour) fast from food and drink (except water) since 10pm the&#xD;
      previous evening. Upon entering the laboratory, body composition (height, weight, waist&#xD;
      circumference) will be assessed and a cannula will be placed into a vein in each arm (one for&#xD;
      infusion of glucose, one for blood sampling). Resting cardiovascular measures (heart rate,&#xD;
      blood pressure, oxygen saturation) will be collected followed by an assessment of cognitive&#xD;
      function followed immediately by one of the four 3.5 hour interventions:&#xD;
&#xD;
        -  Trial A (normoglycaemia prior to exercise): This will involve no glycaemic intervention&#xD;
           and the participant will remain in a rested, normoglycaemic state throughout all&#xD;
           subsequent procedures.&#xD;
&#xD;
        -  Trial B (steady hyperglycaemia prior to exercise): This will involve a continuous&#xD;
           constant-rate glucose infusion to establish a steady hyperglycaemic profile.&#xD;
           Specifically, 1.2g/kg glucose will be infused at a constant infusion rate across 3.5 hrs&#xD;
           (equivalent to 5.71 mg/kg/min).&#xD;
&#xD;
        -  Trial C (fluctuating hyperglycaemia prior to exercise): This will involve repeated&#xD;
           glucose injections so as to cause multiple fluctuations in glycaemia. Specifically, 1.2&#xD;
           g/kg glucose will be infused via 8 equal boluses every 30 minutes across 3.5 hrs (the&#xD;
           equivalent of 0.15 g/kg per bolus infused over 3.5 minutes at a rate of 42.86 mg/kg/min)&#xD;
           interspersed with periods of no infusion.&#xD;
&#xD;
        -  Trial D (normoglycaemia, no exercise): This will be identical to trial A, except there&#xD;
           will be no exercise bout.&#xD;
&#xD;
      After 3.5 hours, the above-described glycaemic intervention will stop, and be followed&#xD;
      immediately by the collection of post-intervention blood samples, assessment of&#xD;
      cardiovascular response and assessment of cognitive function. Participants will then complete&#xD;
      an exercise bout consisting of 45 minutes of moderate intensity (70% HRmax) continuous&#xD;
      cycling, during which energy expenditure will be measured by indirect calorimetry.&#xD;
      Post-exercise blood samples will be collected, and catheters will be removed. Participants&#xD;
      will be fed a meal. Before leaving the lab, they will also be provided with an evening meal&#xD;
      to be consumed at home at 7 pm, and a breakfast and lunch meal for the following day (to be&#xD;
      consumed at 7 am and 12 pm, respectively). Participants will then return to the laboratory&#xD;
      for 5 minutes the afternoon after the trial day (~3 pm) to remove the accelerometer and&#xD;
      continuous glucose monitor, marking the end of the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">December 8, 2018</completion_date>
  <primary_completion_date type="Actual">November 30, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise-induced change in blood glucose control.</measure>
    <time_frame>In all trials, glucose control will be determined between the time-point immediately after exercise and 24 hours after exercise.</time_frame>
    <description>In all trials, continuous glucose monitoring (CGM) will be used to assess the change in glucose control compared to baseline for 24 hours after-exercise, under diet-controlled but otherwise free-living conditions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hyperglycemia-induced change in inflammation.</measure>
    <time_frame>In all trials, inflammation will be determined at baseline (T=0 hours) and at T=3.5 hours. The glycemic interventions take place between baseline (T=0 hours) and T=3.5 hours.</time_frame>
    <description>In all trials, plasma cytokine levels (IL-6, TNF-alpha, IL-1ra) will be measured at baseline (T=0 hours) and immediately after each glycaemic intervention (T=3.5 hours). The interventions will take place between baseline (T=0 hours) and T=3.5 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hyperglycemia-induced change in cognitive function.</measure>
    <time_frame>In all trials, cognitive function will be determined at baseline (T=0 hours) and at T=3.5 hours. The glycemic interventions take place between baseline (T=0 hours) and T=3.5 hours.</time_frame>
    <description>In all trials, cognitive function tests (CANTAB) to measure executive functioning and verbal memory will be administered at baseline (T=0 hours) and immediately after each glycaemic intervention (T=3.5 hours). The interventions will take place between baseline (T=0 hours) and T=3.5 hours.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Aerobic Exercise</condition>
  <condition>Hyperglycemia</condition>
  <condition>Glucose Metabolism Disorders (Including Diabetes Mellitus)</condition>
  <arm_group>
    <arm_group_label>Normal glycemia + exercise</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will be studied in the fasting state under normal blood glucose conditions whereby no glucose will be administered, but an exercise bout will be completed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Steady-state hyperglycemia + exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be studied during experimental steady-state hyperglycemia-induced via a variable-rate intravenous glucose infusion, and an exercise bout will be completed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluctuating hyperglycemia + exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be studied during experimental fluctuating hyperglycemia-induced via repeated intravenous glucose injections, and an exercise bout will be completed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal glycemia, no exercise</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will be studied in the fasting state under normal blood glucose conditions whereby no glucose will be administered and no exercise will be completed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Steady-state hyperglycemia</intervention_name>
    <description>Experimental &quot;diabetic like&quot; steady-state hyperglycemia will be induced via a continuous-rate intravenous glucose infusion.</description>
    <arm_group_label>Steady-state hyperglycemia + exercise</arm_group_label>
    <other_name>Drug (metabolite infusion)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fluctuating hyperglycemia</intervention_name>
    <description>Experimental &quot;diabetic like&quot; fluctuating hyperglycemia will be induced via repeated intravenous glucose injections.</description>
    <arm_group_label>Fluctuating hyperglycemia + exercise</arm_group_label>
    <other_name>Drug (metabolite injection)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Moderate-intensity exercise bout (45-minutes of cycling at 70% of their heart rate max) at T=4.5 hours</description>
    <arm_group_label>Fluctuating hyperglycemia + exercise</arm_group_label>
    <arm_group_label>Normal glycemia + exercise</arm_group_label>
    <arm_group_label>Steady-state hyperglycemia + exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Aged between 18 and 50 years.&#xD;
&#xD;
          -  Body Mass Index of between 19 and 30 kg/m2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking.&#xD;
&#xD;
          -  Regularly use of anti-inflammatory medication.&#xD;
&#xD;
          -  More than 2 kg weight change in the last 6 months, and/or have undergone weight loss&#xD;
             surgery.&#xD;
&#xD;
          -  Previous or current cancer or chronic haematological, pulmonary, cardiac, hepatic,&#xD;
             renal, metabolic, or gastrointestinal diseases.&#xD;
&#xD;
          -  Currently engaged in moderate or vigorous exercise on more than 5 days per week.&#xD;
&#xD;
          -  Contraindication to exercise.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas P Solomon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2TT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>February 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>December 10, 2018</last_update_submitted>
  <last_update_submitted_qc>December 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperglycemia</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</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/NCT03284216
org study id: ERN_16-0193
nct id: NCT03284216
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will determine whether exposure to short-term high blood glucose levels impairs
      exercise-induced adaptations in glucose tolerance, and whether the pattern of high blood
      glucose levels plays a role.
Healthy male volunteers will undergo a screening visit and four experimental trials.

      Screening Visit: Having read the participant info sheet, a study investigator will discuss
      the project with the potential participant who will have the chance to ask any questions.
      Informed consent will be sought and a General Health Questionnaire will be completed. Body
      weight, height, and skinfold measurements will be taken. Participants will also complete an
      exercise test to measure V̇O2max test along with heart rate and blood pressure measurements.

      Individuals eligible for inclusion in the study will then return to the lab for four
      experimental trials, each separated by ~1 week. Trials will be completed using a randomised,
      counter-balanced, cross-over design. Between experimental trials, participants will be
      instructed to maintain their normal diet and activity habits. During the 48 hours prior to
      each experimental trial participants will be instructed to refrain from vigorous exercise and
      alcohol. For 3 days prior to each experimental trial, participants will record their dietary
      intake, and wear an accelerometer and a continuous glucose monitor to measure physical
      activity levels and glucose control.

      Experimental Trials: Participants will arrive at the laboratory in the morning (~8 am)
      following an overnight (~10 hour) fast from food and drink (except water) since 10pm the
      previous evening. Upon entering the laboratory, body composition (height, weight, waist
      circumference) will be assessed and a cannula will be placed into a vein in each arm (one for
      infusion of glucose, one for blood sampling). Resting cardiovascular measures (heart rate,
      blood pressure, oxygen saturation) will be collected followed by an assessment of cognitive
      function followed immediately by one of the four 3.5 hour interventions:

        -  Trial A (normoglycaemia prior to exercise): This will involve no glycaemic intervention
           and the participant will remain in a rested, normoglycaemic state throughout all
           subsequent procedures.

        -  Trial B (steady hyperglycaemia prior to exercise): This will involve a continuous
           constant-rate glucose infusion to establish a steady hyperglycaemic profile.
           Specifically, 1.2g/kg glucose will be infused at a constant infusion rate across 3.5 hrs
           (equivalent to 5.71 mg/kg/min).

        -  Trial C (fluctuating hyperglycaemia prior to exercise): This will involve repeated
           glucose injections so as to cause multiple fluctuations in glycaemia. Specifically, 1.2
           g/kg glucose will be infused via 8 equal boluses every 30 minutes across 3.5 hrs (the
           equivalent of 0.15 g/kg per bolus infused over 3.5 minutes at a rate of 42.86 mg/kg/min)
           interspersed with periods of no infusion.

        -  Trial D (normoglycaemia, no exercise): This will be identical to trial A, except there
           will be no exercise bout.

      After 3.5 hours, the above-described glycaemic intervention will stop, and be followed
      immediately by the collection of post-intervention blood samples, assessment of
      cardiovascular response and assessment of cognitive function. Participants will then complete
      an exercise bout consisting of 45 minutes of moderate intensity (70% HRmax) continuous
      cycling, during which energy expenditure will be measured by indirect calorimetry.
      Post-exercise blood samples will be collected, and catheters will be removed. Participants
      will be fed a meal. Before leaving the lab, they will also be provided with an evening meal
      to be consumed at home at 7 pm, and a breakfast and lunch meal for the following day (to be
      consumed at 7 am and 12 pm, respectively). Participants will then return to the laboratory
      for 5 minutes the afternoon after the trial day (~3 pm) to remove the accelerometer and
      continuous glucose monitor, marking the end of the trial.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Exercise-induced change in blood glucose control.
time frame: In all trials, glucose control will be determined between the time-point immediately after exercise and 24 hours after exercise.
description: In all trials, continuous glucose monitoring (CGM) will be used to assess the change in glucose control compared to baseline for 24 hours after-exercise, under diet-controlled but otherwise free-living conditions.
measure: Hyperglycemia-induced change in inflammation.
time frame: In all trials, inflammation will be determined at baseline (T=0 hours) and at T=3.5 hours. The glycemic interventions take place between baseline (T=0 hours) and T=3.5 hours.
description: In all trials, plasma cytokine levels (IL-6, TNF-alpha, IL-1ra) will be measured at baseline (T=0 hours) and immediately after each glycaemic intervention (T=3.5 hours). The interventions will take place between baseline (T=0 hours) and T=3.5 hours.
measure: Hyperglycemia-induced change in cognitive function.
time frame: In all trials, cognitive function will be determined at baseline (T=0 hours) and at T=3.5 hours. The glycemic interventions take place between baseline (T=0 hours) and T=3.5 hours.
description: In all trials, cognitive function tests (CANTAB) to measure executive functioning and verbal memory will be administered at baseline (T=0 hours) and immediately after each glycaemic intervention (T=3.5 hours). The interventions will take place between baseline (T=0 hours) and T=3.5 hours.
arm group label: Normal glycemia + exercise
arm group type: Other
description: Participants will be studied in the fasting state under normal blood glucose conditions whereby no glucose will be administered, but an exercise bout will be completed.
arm group label: Steady-state hyperglycemia + exercise
arm group type: Experimental
description: Participants will be studied during experimental steady-state hyperglycemia-induced via a variable-rate intravenous glucose infusion, and an exercise bout will be completed.
arm group label: Fluctuating hyperglycemia + exercise
arm group type: Experimental
description: Participants will be studied during experimental fluctuating hyperglycemia-induced via repeated intravenous glucose injections, and an exercise bout will be completed.
arm group label: Normal glycemia, no exercise
arm group type: No Intervention
description: Participants will be studied in the fasting state under normal blood glucose conditions whereby no glucose will be administered and no exercise will be completed.
intervention type: Procedure
intervention name: Steady-state hyperglycemia
description: Experimental "diabetic like" steady-state hyperglycemia will be induced via a continuous-rate intravenous glucose infusion.
arm group label: Steady-state hyperglycemia + exercise
other name: Drug (metabolite infusion)
intervention type: Procedure
intervention name: Fluctuating hyperglycemia
description: Experimental "diabetic like" fluctuating hyperglycemia will be induced via repeated intravenous glucose injections.
arm group label: Fluctuating hyperglycemia + exercise
other name: Drug (metabolite injection)
intervention type: Behavioral
intervention name: Exercise
description: Moderate-intensity exercise bout (45-minutes of cycling at 70% of their heart rate max) at T=4.5 hours
arm group label: Fluctuating hyperglycemia + exercise
arm group label: Normal glycemia + exercise
arm group label: Steady-state hyperglycemia + exercise
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Thomas P Solomon, PhD
role: Principal Investigator
affiliation: University of Birmingham
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Hyperglycemia
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders
sharing ipd: Undecided