<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/NCT04472962</url>
  </required_header>
  <id_info>
    <org_study_id>H-20007316</org_study_id>
    <nct_id>NCT04472962</nct_id>
  </id_info>
  <brief_title>The Importance of Meal Composition on Preventing Exercise-induced Hypoglycemia in People With Type 1 Diabetes.</brief_title>
  <official_title>The Effect of a Low-carbohydrate-high-protein Pre-exercise Meal on Exercise-induced Hypoglycemia in People With Type 1 Diabetes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Steno Diabetes Center Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swansea University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Steno Diabetes Center Copenhagen</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 is a clinical, randomized, crossover study. The study investigates the effect of a&#xD;
      low-carbohydrate-high-protein pre-exercise meal on preventing exercise-induced hypoglycemia&#xD;
      in people with type 1 diabetes. The hypothesis is that intake of a&#xD;
      low-carbohydrate-high-protein meal can reduce the duration and depth of hypoglycemia during&#xD;
      and after exercise in people with type 1 diabetes compared with an isocaloric&#xD;
      high-carbohydrate-low-protein meal with identical fat content. The study will contribute with&#xD;
      new knowledge about importance of meal composition on preventing exercise-induced&#xD;
      hypoglycemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      People with type 1 diabetes practicing a low-carbohydrate diet can increase the fat and/or&#xD;
      protein content of the diet to cover their energy needs. In relation to physical activity,&#xD;
      ingestion of protein is preferable for muscle protein synthesis and enhances structural&#xD;
      changes in non-muscle tissues such as tendons and bones. Furthermore, addition of ≥ 28 g of&#xD;
      protein to a meal is likely to result in significant and sustained postprandial hyperglycemia&#xD;
      commencing in the late postprandial period (2-3 h) and continuing beyond 5 h in people with&#xD;
      type 1 diabetes. The protein-induced change in the postprandial glucose response could be&#xD;
      beneficial in relation to prevention of exercise-induced hypoglycemia. Hypoglycemia is a&#xD;
      common fear in people with type 1 diabetes and makes many abstain from exercising.&#xD;
&#xD;
      This study investigates the effect of a low-carbohydrate-high-protein pre-exercise meal on&#xD;
      preventing exercise-induced hypoglycemia in people with type 1 diabetes. The hypothesis is&#xD;
      that intake of a low-carbohydrate-high-protein meal can reduce the duration and depth of&#xD;
      hypoglycemia during and after exercise in people with type 1 diabetes compared with an&#xD;
      isocaloric high-carbohydrate-low-protein meal with identical fat content.&#xD;
&#xD;
      This study will contribute with new knowledge about importance of meal composition on&#xD;
      preventing exercise-induced hypoglycemia. The study may add new aspects to current guidelines&#xD;
      for glucose management during exercise in people with type 1 diabetes. If the strategy has a&#xD;
      positive effect on preventing exercise-induced hypoglycemia it will be useful to all people&#xD;
      with type 1 diabetes irrespective of diet strategy.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      The study is a randomized, two-arm crossover trial including one screening visit, two study&#xD;
      days and a short visit after each study day, where the participants must meet to upload&#xD;
      research data. The study will include adults with type 1 diabetes on insulin pump therapy&#xD;
      using flash glucose monitoring (FGM) or continuous glucose monitoring (CGM). 15 participants&#xD;
      have to complete the study. The study days are identical except for the content of the&#xD;
      pre-exercise meal (low-carbohydrate-high-protein meal versus high-carbohydrate-low-protein&#xD;
      meal) and the size of the meal bolus. Meals are isocaloric. The participants will complete&#xD;
      two study days in random order with a 10-14 days washout period between. 48 hours prior to&#xD;
      each study day blood glucose will be monitored by CGM and activity level will be monitored by&#xD;
      an activity monitor wristband.&#xD;
&#xD;
      Each study day is divided into an in-clinic period, which takes place at Steno Diabetes&#xD;
      Center Copenhagen (SDCC), and a home period, which takes place in the participants own homes.&#xD;
&#xD;
      The participants will arrive at the research facility in the morning following an overnight&#xD;
      fast. A pre-exercise meal with either low-carbohydrate-high-protein content or&#xD;
      high-carbohydrate-low-protein content will be served. To estimate the gastric emptying 1g&#xD;
      paracetamol will be added to the meal. After ingesting the meal and 90 min of resting the&#xD;
      participants must perform 45 min of exercise on an ergometer cycle equaling to 60 % of their&#xD;
      peak oxygen consumption or until hypoglycemia (plasma glucose &lt; 3.9) or unbearable symptoms&#xD;
      of hypoglycemia. Throughout the in-clinic study day the participants must use their insulin&#xD;
      pumps. The basal insulin rate and meal-bolus will be adjusted according to international&#xD;
      guidelines. Blood samples for analysis of glucose, insulin, glucagon, cortisol, adrenalin,&#xD;
      noradrenalin, growth hormone, ketones, lactate, free fatty acids, GLP1, GIP and inflammatory&#xD;
      markers will be collected. Indirect calorimetry will be performed before, during and after&#xD;
      exercise to measure energy expenditure, respiratory exchange ratio and carbohydrate and fat&#xD;
      oxidation rates. The Borg Scale will be used to assess perceived exertion during the exercise&#xD;
      and a visual analog scale will be used to assess the feeling of satiety during the study day.&#xD;
&#xD;
      Leaving SDCC the home period begins. Throughout the home period the blood glucose and&#xD;
      activity level will be monitored by the CGM and the activity monitor until the next morning,&#xD;
      where the study day ends. From the research facility the participants will be provided a&#xD;
      standard evening meal and a bedtime snack. The participants will also be provided dextrose&#xD;
      tablets, which they must ingest in case of hypoglycemia. Within one week after both study&#xD;
      days, the participants must meet at the clinic to upload research data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Actual">January 30, 2021</completion_date>
  <primary_completion_date type="Actual">January 30, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The area over the curve (AOC).</measure>
    <time_frame>7 hours.</time_frame>
    <description>The primary outcome measure is the AOC for plasma glucose (PG) &lt; 3.9 mmol/L during the in-clinic period assessed by YSI (Yellow Spring Instruments 2900 STAT Plus). The AOC is the area, which extends from the plasma glucose curve to the limit for hypoglycemia &lt; 3.9 mmol/l.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time spent &lt; 3.9 mmol/l during in-clinic period, home period and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &lt; 3.9 mmol/l during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent 3.0-3.8 mmol/l during in-clinic period, home period, and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent 3.0-3.8 mmol/l during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &lt; 3.0 mmol/l during in-clinic period, home period, and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &lt; 3.0 mmol/l during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent 3.9-10.0 mmol/l during in-clinic period, home period and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &gt; 10.0 mmol/l during in-clinic period, home period and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &gt; 10.0 during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &gt; 13.9 during in-clinic period, home period and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent &gt; 13.9 during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycemic variability (% coefficient of variation) during in-clinic, home, and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycemic variability (% coefficient of variation) during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standard deviation (SD) during in-clinic period, home period, and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standard deviation (SD) during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hypoglycemia events (&lt; 3.9 mmol/l) in-clinic period, home period and overall study period assessed by CGM.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hypoglycemia events (&lt; 3.9 mmol/l) during in-clinic period assessed by YSI.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of dextrose in grams ingested to treat hypoglycemia (&lt; 3.9 mmol/l) during in-clinic period, home period and overall study period.</measure>
    <time_frame>7, 17 and 24 hours respectively.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak PG/blood glucose after ingestion of pre-exercise meal assessed by YSI and CGM.</measure>
    <time_frame>3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-to-peak PG/blood glucose after ingestion of pre-exercise meal assessed by YSI and CGM</measure>
    <time_frame>3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of total insulin during in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of glucagon during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of cortisol during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of growth hormone during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of epinephrine during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of norepinephrine during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of lactate during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of free fatty acids during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of ketones during the in-clinic period.</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of GLP-1 during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of GIP during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of IL6 during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of IL-1ra during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of IL-10 during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of TNFα during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of IL-1β during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory exchange ratio (RER) during the in-clinic period</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Energy expenditure during the in-clinic period (kcal/min)</measure>
    <time_frame>7 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carbohydrate and fat oxidation rates during the in-clinic period</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of gastric emptying after ingestion of the pre-exercise meal assessed by serum paracetamol.</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical performance during the exercise phase evaluated by heart rate</measure>
    <time_frame>45 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical performance during the exercise phase evaluated by watt</measure>
    <time_frame>45 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feeling of physical hardness during the exercise phase evaluated using the Borg Scale.</measure>
    <time_frame>45 minutes.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satiety (assessed by visual analog scale after pre-exercise meal) during the in-clinic period</measure>
    <time_frame>7 hours.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Low-carbohydrate-high-protein pre-exercise meal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High-carbohydrate-low-protein pre-exercise meal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pre-exercise meal</intervention_name>
    <description>Mixed meal with low-carbohydrate-high-protein content</description>
    <arm_group_label>Low-carbohydrate-high-protein pre-exercise meal</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pre-exercise meal</intervention_name>
    <description>Mixed meal with high-carbohydrate-low-protein content</description>
    <arm_group_label>High-carbohydrate-low-protein pre-exercise meal</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70 years.&#xD;
&#xD;
          -  Type 1 diabetes ≥ 5 years.&#xD;
&#xD;
          -  Insulin pump use ≥ 1 year.&#xD;
&#xD;
          -  Use of flash glucose monitoring (FGM) or continuous glucose monitoring (CGM) ≥ 3&#xD;
             months.&#xD;
&#xD;
          -  Body mass index 18.5-30 kg/m2.&#xD;
&#xD;
          -  HbA1c ≤ 64 mmol/mol (8.0%).&#xD;
&#xD;
          -  Self-reported hypoglycemia awareness&#xD;
&#xD;
          -  Ability to carbohydrate count for all meals.&#xD;
&#xD;
          -  Familiarity with the insulin pump bolus calculator for all meals.&#xD;
&#xD;
          -  Moderate to vigorous level of physical activity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs&#xD;
             affecting glucose metabolism during the study period or within 30 days prior to study&#xD;
             start.&#xD;
&#xD;
          -  Use of Metronic Minimed 670G insulin pump system.&#xD;
&#xD;
          -  Allergy to paracetamol or nuts&#xD;
&#xD;
          -  Females who are pregnant, breast-feeding or intend to become pregnant.&#xD;
&#xD;
          -  Heart disease.&#xD;
&#xD;
          -  Severe asthma.&#xD;
&#xD;
          -  Other concomitant medical or psychological condition that according to the&#xD;
             investigator's assessment makes the individual unsuitable for study participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Steno Diabetes Center Copenhagen</name>
      <address>
        <city>Gentofte</city>
        <zip>2820</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>February 12, 2021</last_update_submitted>
  <last_update_submitted_qc>February 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Exercise</keyword>
  <keyword>Nutrition</keyword>
  <keyword>Hypoglycemia</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 1</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <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/NCT04472962
org study id: H-20007316
nct id: NCT04472962
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a clinical, randomized, crossover study. The study investigates the effect of a
      low-carbohydrate-high-protein pre-exercise meal on preventing exercise-induced hypoglycemia
      in people with type 1 diabetes. The hypothesis is that intake of a
      low-carbohydrate-high-protein meal can reduce the duration and depth of hypoglycemia during
      and after exercise in people with type 1 diabetes compared with an isocaloric
      high-carbohydrate-low-protein meal with identical fat content. The study will contribute with
      new knowledge about importance of meal composition on preventing exercise-induced
      hypoglycemia.
Background:

      People with type 1 diabetes practicing a low-carbohydrate diet can increase the fat and/or
      protein content of the diet to cover their energy needs. In relation to physical activity,
      ingestion of protein is preferable for muscle protein synthesis and enhances structural
      changes in non-muscle tissues such as tendons and bones. Furthermore, addition of ≥ 28 g of
      protein to a meal is likely to result in significant and sustained postprandial hyperglycemia
      commencing in the late postprandial period (2-3 h) and continuing beyond 5 h in people with
      type 1 diabetes. The protein-induced change in the postprandial glucose response could be
      beneficial in relation to prevention of exercise-induced hypoglycemia. Hypoglycemia is a
      common fear in people with type 1 diabetes and makes many abstain from exercising.

      This study investigates the effect of a low-carbohydrate-high-protein pre-exercise meal on
      preventing exercise-induced hypoglycemia in people with type 1 diabetes. The hypothesis is
      that intake of a low-carbohydrate-high-protein meal can reduce the duration and depth of
      hypoglycemia during and after exercise in people with type 1 diabetes compared with an
      isocaloric high-carbohydrate-low-protein meal with identical fat content.

      This study will contribute with new knowledge about importance of meal composition on
      preventing exercise-induced hypoglycemia. The study may add new aspects to current guidelines
      for glucose management during exercise in people with type 1 diabetes. If the strategy has a
      positive effect on preventing exercise-induced hypoglycemia it will be useful to all people
      with type 1 diabetes irrespective of diet strategy.

      Study design:

      The study is a randomized, two-arm crossover trial including one screening visit, two study
      days and a short visit after each study day, where the participants must meet to upload
      research data. The study will include adults with type 1 diabetes on insulin pump therapy
      using flash glucose monitoring (FGM) or continuous glucose monitoring (CGM). 15 participants
      have to complete the study. The study days are identical except for the content of the
      pre-exercise meal (low-carbohydrate-high-protein meal versus high-carbohydrate-low-protein
      meal) and the size of the meal bolus. Meals are isocaloric. The participants will complete
      two study days in random order with a 10-14 days washout period between. 48 hours prior to
      each study day blood glucose will be monitored by CGM and activity level will be monitored by
      an activity monitor wristband.

      Each study day is divided into an in-clinic period, which takes place at Steno Diabetes
      Center Copenhagen (SDCC), and a home period, which takes place in the participants own homes.

      The participants will arrive at the research facility in the morning following an overnight
      fast. A pre-exercise meal with either low-carbohydrate-high-protein content or
      high-carbohydrate-low-protein content will be served. To estimate the gastric emptying 1g
      paracetamol will be added to the meal. After ingesting the meal and 90 min of resting the
      participants must perform 45 min of exercise on an ergometer cycle equaling to 60 % of their
      peak oxygen consumption or until hypoglycemia (plasma glucose < 3.9) or unbearable symptoms
      of hypoglycemia. Throughout the in-clinic study day the participants must use their insulin
      pumps. The basal insulin rate and meal-bolus will be adjusted according to international
      guidelines. Blood samples for analysis of glucose, insulin, glucagon, cortisol, adrenalin,
      noradrenalin, growth hormone, ketones, lactate, free fatty acids, GLP1, GIP and inflammatory
      markers will be collected. Indirect calorimetry will be performed before, during and after
      exercise to measure energy expenditure, respiratory exchange ratio and carbohydrate and fat
      oxidation rates. The Borg Scale will be used to assess perceived exertion during the exercise
      and a visual analog scale will be used to assess the feeling of satiety during the study day.

      Leaving SDCC the home period begins. Throughout the home period the blood glucose and
      activity level will be monitored by the CGM and the activity monitor until the next morning,
      where the study day ends. From the research facility the participants will be provided a
      standard evening meal and a bedtime snack. The participants will also be provided dextrose
      tablets, which they must ingest in case of hypoglycemia. Within one week after both study
      days, the participants must meet at the clinic to upload research data.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The area over the curve (AOC).
time frame: 7 hours.
description: The primary outcome measure is the AOC for plasma glucose (PG) < 3.9 mmol/L during the in-clinic period assessed by YSI (Yellow Spring Instruments 2900 STAT Plus). The AOC is the area, which extends from the plasma glucose curve to the limit for hypoglycemia < 3.9 mmol/l.
measure: Time spent < 3.9 mmol/l during in-clinic period, home period and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent < 3.9 mmol/l during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Time spent 3.0-3.8 mmol/l during in-clinic period, home period, and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent 3.0-3.8 mmol/l during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Time spent < 3.0 mmol/l during in-clinic period, home period, and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent < 3.0 mmol/l during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Time spent 3.9-10.0 mmol/l during in-clinic period, home period and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent > 10.0 mmol/l during in-clinic period, home period and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent > 10.0 during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Time spent > 13.9 during in-clinic period, home period and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Time spent > 13.9 during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Glycemic variability (% coefficient of variation) during in-clinic, home, and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Glycemic variability (% coefficient of variation) during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Standard deviation (SD) during in-clinic period, home period, and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Standard deviation (SD) during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Number of hypoglycemia events (< 3.9 mmol/l) in-clinic period, home period and overall study period assessed by CGM.
time frame: 7, 17 and 24 hours respectively.
measure: Number of hypoglycemia events (< 3.9 mmol/l) during in-clinic period assessed by YSI.
time frame: 7 hours.
measure: Amount of dextrose in grams ingested to treat hypoglycemia (< 3.9 mmol/l) during in-clinic period, home period and overall study period.
time frame: 7, 17 and 24 hours respectively.
measure: Peak PG/blood glucose after ingestion of pre-exercise meal assessed by YSI and CGM.
time frame: 3 hours
measure: Time-to-peak PG/blood glucose after ingestion of pre-exercise meal assessed by YSI and CGM
time frame: 3 hours
measure: Area under the curve of total insulin during in-clinic period
time frame: 7 hours
measure: Area under the curve of glucagon during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of cortisol during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of growth hormone during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of epinephrine during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of norepinephrine during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of lactate during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of free fatty acids during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of ketones during the in-clinic period.
time frame: 7 hours
measure: Area under the curve of GLP-1 during the in-clinic period
time frame: 7 hours
measure: Area under the curve of GIP during the in-clinic period
time frame: 7 hours
measure: Area under the curve of IL6 during the in-clinic period
time frame: 7 hours
measure: Area under the curve of IL-1ra during the in-clinic period
time frame: 7 hours
measure: Area under the curve of IL-10 during the in-clinic period
time frame: 7 hours
measure: Area under the curve of TNFα during the in-clinic period
time frame: 7 hours
measure: Area under the curve of IL-1β during the in-clinic period
time frame: 7 hours
measure: Respiratory exchange ratio (RER) during the in-clinic period
time frame: 7 hours
measure: Energy expenditure during the in-clinic period (kcal/min)
time frame: 7 hours
measure: Carbohydrate and fat oxidation rates during the in-clinic period
time frame: 7 hours.
measure: Time of gastric emptying after ingestion of the pre-exercise meal assessed by serum paracetamol.
time frame: 7 hours.
measure: Physical performance during the exercise phase evaluated by heart rate
time frame: 45 minutes
measure: Physical performance during the exercise phase evaluated by watt
time frame: 45 minutes
measure: Feeling of physical hardness during the exercise phase evaluated using the Borg Scale.
time frame: 45 minutes.
measure: Satiety (assessed by visual analog scale after pre-exercise meal) during the in-clinic period
time frame: 7 hours.
arm group label: Low-carbohydrate-high-protein pre-exercise meal
arm group type: Active Comparator
arm group label: High-carbohydrate-low-protein pre-exercise meal
arm group type: Active Comparator
intervention type: Other
intervention name: Pre-exercise meal
description: Mixed meal with low-carbohydrate-high-protein content
arm group label: Low-carbohydrate-high-protein pre-exercise meal
intervention type: Other
intervention name: Pre-exercise meal
description: Mixed meal with high-carbohydrate-low-protein content
arm group label: High-carbohydrate-low-protein pre-exercise meal
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemia
sharing ipd: No