<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/NCT03773731</url>
  </required_header>
  <id_info>
    <org_study_id>Exercise_platelet_insulin</org_study_id>
    <nct_id>NCT03773731</nct_id>
  </id_info>
  <brief_title>High Intensity Interval Training in Prediabetes</brief_title>
  <official_title>Impact of High Intensity Interval Training vs. Continuous Aerobic Training on Platelet Insulin Resistance, Platelet Function and Hepatic Steatosis in Patients With Prediabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Vienna, Institute for Sport Science</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanatorium Hera Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Vienna</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 trial investigates if high intensity interval training is more effective than moderate&#xD;
      intensity continuous training in suppressing platelet reactivity and hepatic fat content in&#xD;
      prediabetic individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      The prevalence of type 2 diabetes mellitus (T2DM) is rising dramatically. T2DM represents a&#xD;
      major cause for cardiovascular disease -related mortality and morbidity and increasingly&#xD;
      burdens healthcare systems. While the fundamental pathomechanism of T2DM is insulin&#xD;
      resistance of muscle and adipose tissue, recent studies demonstrate that insulin resistance&#xD;
      in T2DM also occurs in platelets. As insulin directly inhibits platelet function, this&#xD;
      mechanism might contribute to platelet activation and platelet hyperreactivity, which were in&#xD;
      fact detected in diabetic patients. Since (inadvertent) platelet activation is causally&#xD;
      linked to the development of atherosclerosis and atherothrombosis, regulation of platelet&#xD;
      function is of utmost importance. Exercise training, performed on a regular basis has been&#xD;
      shown to reduce morbidity and mortality in sedentary and diseased populations. Furthermore,&#xD;
      exercise training improves whole body insulin sensitivity - however, it is currently unclear,&#xD;
      if exercise training also affects insulin sensitivity of platelets. Recently, a time-saving&#xD;
      interval training protocol has been adapted for T2DM-patients. Since this adapted high&#xD;
      intensity interval training (HIIT) needs a fractional time commitment of exercise training&#xD;
      according to current guidelines, HIIT possibly represents a promising instrument to increase&#xD;
      adherence to exercise and thereby reduce T2DM morbidity.&#xD;
&#xD;
      Aims:&#xD;
&#xD;
      The primary aim of this study is to investigate the effect of 12 weeks of HIIT vs. continuous&#xD;
      training (CT) on platelet insulin sensitivity and platelet (hyper)reactivity in prediabetic&#xD;
      patients.&#xD;
&#xD;
      Secondary aims are to assess the effect of HIIT and CT on whole body insulin sensitivity and&#xD;
      fitness in prediabetic patients as well as on various parameters of platelet function and on&#xD;
      the hepatic fat content.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      Our main hypothesis is that HIIT increases platelet insulin sensitivity and thereby decreases&#xD;
      platelet activation/reactivity in patients with prediabetes. Methods: 44 prediabetic (see&#xD;
      inclusion criteria) patients will be enrolled in this study. Patients will randomly be&#xD;
      assigned to a HIIT group (committed to a supervised training program) or a CT group. After&#xD;
      initial examinations (supervised graded exercise test, platelet function tests, oral glucose&#xD;
      tolerance test, measurement of the hepatic fat content via FibroScan®), supervised training&#xD;
      will be performed over a period of 12 weeks. Tests performed at the beginning of the study&#xD;
      will be repeated after the training period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 4, 2019</start_date>
  <completion_date type="Anticipated">February 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>EC50 (half-maximal effective concentration) of TRAP-6 (thrombin-receptor activating peptide) in terms of surface CD62P (=platelet selectin, P-selectin) expression: group differences after 12 weeks of training</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>EC50 of insulin in terms of intraplatelet VASP (vasodilator-stimulated phosphoprotein)-phosphorylation: group differences after 12 weeks of training</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>whole body insulin sensitivity</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal oxygen consumption</measure>
    <time_frame>12 weeks</time_frame>
    <description>Unit: ml/min/kg bodymass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EC50 of other platelet agonists in terms of various platelet activation markers</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EC50 of prostacyclin in terms of intraplatelet VASP-phosphorylation</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transient elastography (FibroScan®) controlled attenuation parameter (CAP)</measure>
    <time_frame>12 weeks</time_frame>
    <description>The controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatty Liver Index (FLI)</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Prediabetic State</condition>
  <arm_group>
    <arm_group_label>High intensity interval training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks:&#xD;
5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test&#xD;
30 minutes: intensive cycling bouts of 60s interspersed with 60s of recovery intervals. Power output will be 90% (week 1-6) or 95% (week 7-12) of the maximal power output of the exercise test during the intensive cycling bouts. During recovery intervals, subjects will pedal with a power output of 30% (week 1-6) or 35% (week 7-12) of the maximal power output of the exercise test.&#xD;
10 minutes with 30% of maximal power output.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate intensity continuous training</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks:&#xD;
5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test&#xD;
30 minutes: Continuous training with 60% (week 1-6) or 65% (week 7-12) of maximal power output&#xD;
10 minutes with 30% of maximal power output.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>High intensity interval training (HIIT)</intervention_name>
    <description>Exercise training on bicycle ergometer with high intensity bouts of 1 min interspersed by low intensity recovery intervals</description>
    <arm_group_label>High intensity interval training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Moderate intensity continuous training (MICT)</intervention_name>
    <description>Exercise training on bicycle ergometer with moderate intensity (60 - 65 % of individual maximal power output)</description>
    <arm_group_label>Moderate intensity continuous training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  prediabetic (insulin-insensitive) patients&#xD;
&#xD;
          -  either fasting plasma glucose 100- 125 mg/dl or HbA1c 5.7 - 6.4&#xD;
&#xD;
          -  &lt; 3kg bodyweight change within the last 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contraindications for exercise&#xD;
&#xD;
          -  resulting from anamnesis ( e.g. history of angina pectoris, peripheral arterial&#xD;
             disease), ECG at rest or during graded exercise test, echocardiogram, echocardiography&#xD;
             or lung function test&#xD;
&#xD;
          -  chronical joint pain that makes exercise training on bicycle ergometers impossible&#xD;
&#xD;
          -  any conditions that make the successful participation in the study unlikely&#xD;
&#xD;
          -  islet cell autoantibodies&#xD;
&#xD;
          -  Medication: insulin, thiazolidindiones, statins, antidepressants&#xD;
&#xD;
          -  Secondary diseases: History of end-stage liver or kidney disease; pronounced&#xD;
             neuropathy or retinopathy&#xD;
&#xD;
          -  drug or alcohol abuse&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ivo Volf, PhD</last_name>
    <phone>+43 40160</phone>
    <phone_ext>31421</phone_ext>
    <email>ivo.volf@meduniwien.ac.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rochus Pokan, MD</last_name>
    <phone>+43 4277 4887225</phone>
    <email>rochus.pokan@univie.ac.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>MUVienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefan Heber, MD, PhD</last_name>
      <phone>0043 1 40160</phone>
      <phone_ext>31425</phone_ext>
      <email>stefan.heber@meduniwien.ac.at</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>January 7, 2019</last_update_submitted>
  <last_update_submitted_qc>January 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Stefan Heber</investigator_full_name>
    <investigator_title>Dr.med.univ. Dr.rer.nat.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prediabetic State</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/NCT03773731
org study id: Exercise_platelet_insulin
nct id: NCT03773731
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This trial investigates if high intensity interval training is more effective than moderate
      intensity continuous training in suppressing platelet reactivity and hepatic fat content in
      prediabetic individuals.
Background:

      The prevalence of type 2 diabetes mellitus (T2DM) is rising dramatically. T2DM represents a
      major cause for cardiovascular disease -related mortality and morbidity and increasingly
      burdens healthcare systems. While the fundamental pathomechanism of T2DM is insulin
      resistance of muscle and adipose tissue, recent studies demonstrate that insulin resistance
      in T2DM also occurs in platelets. As insulin directly inhibits platelet function, this
      mechanism might contribute to platelet activation and platelet hyperreactivity, which were in
      fact detected in diabetic patients. Since (inadvertent) platelet activation is causally
      linked to the development of atherosclerosis and atherothrombosis, regulation of platelet
      function is of utmost importance. Exercise training, performed on a regular basis has been
      shown to reduce morbidity and mortality in sedentary and diseased populations. Furthermore,
      exercise training improves whole body insulin sensitivity - however, it is currently unclear,
      if exercise training also affects insulin sensitivity of platelets. Recently, a time-saving
      interval training protocol has been adapted for T2DM-patients. Since this adapted high
      intensity interval training (HIIT) needs a fractional time commitment of exercise training
      according to current guidelines, HIIT possibly represents a promising instrument to increase
      adherence to exercise and thereby reduce T2DM morbidity.

      Aims:

      The primary aim of this study is to investigate the effect of 12 weeks of HIIT vs. continuous
      training (CT) on platelet insulin sensitivity and platelet (hyper)reactivity in prediabetic
      patients.

      Secondary aims are to assess the effect of HIIT and CT on whole body insulin sensitivity and
      fitness in prediabetic patients as well as on various parameters of platelet function and on
      the hepatic fat content.

      Hypotheses:

      Our main hypothesis is that HIIT increases platelet insulin sensitivity and thereby decreases
      platelet activation/reactivity in patients with prediabetes. Methods: 44 prediabetic (see
      inclusion criteria) patients will be enrolled in this study. Patients will randomly be
      assigned to a HIIT group (committed to a supervised training program) or a CT group. After
      initial examinations (supervised graded exercise test, platelet function tests, oral glucose
      tolerance test, measurement of the hepatic fat content via FibroScan®), supervised training
      will be performed over a period of 12 weeks. Tests performed at the beginning of the study
      will be repeated after the training period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Investigator, Outcomes Assessor)
measure: EC50 (half-maximal effective concentration) of TRAP-6 (thrombin-receptor activating peptide) in terms of surface CD62P (=platelet selectin, P-selectin) expression: group differences after 12 weeks of training
time frame: 12 weeks
measure: EC50 of insulin in terms of intraplatelet VASP (vasodilator-stimulated phosphoprotein)-phosphorylation: group differences after 12 weeks of training
time frame: 12 weeks
measure: whole body insulin sensitivity
time frame: 12 weeks
measure: Maximal oxygen consumption
time frame: 12 weeks
description: Unit: ml/min/kg bodymass
measure: EC50 of other platelet agonists in terms of various platelet activation markers
time frame: 12 weeks
measure: EC50 of prostacyclin in terms of intraplatelet VASP-phosphorylation
time frame: 12 weeks
measure: Transient elastography (FibroScan®) controlled attenuation parameter (CAP)
time frame: 12 weeks
description: The controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD
measure: Fatty Liver Index (FLI)
time frame: 12 weeks
arm group label: High intensity interval training
arm group type: Experimental
description: 3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks:
5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test
30 minutes: intensive cycling bouts of 60s interspersed with 60s of recovery intervals. Power output will be 90% (week 1-6) or 95% (week 7-12) of the maximal power output of the exercise test during the intensive cycling bouts. During recovery intervals, subjects will pedal with a power output of 30% (week 1-6) or 35% (week 7-12) of the maximal power output of the exercise test.
10 minutes with 30% of maximal power output.
arm group label: Moderate intensity continuous training
arm group type: Active Comparator
description: 3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks:
5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test
30 minutes: Continuous training with 60% (week 1-6) or 65% (week 7-12) of maximal power output
10 minutes with 30% of maximal power output.
intervention type: Behavioral
intervention name: High intensity interval training (HIIT)
description: Exercise training on bicycle ergometer with high intensity bouts of 1 min interspersed by low intensity recovery intervals
arm group label: High intensity interval training
intervention type: Behavioral
intervention name: Moderate intensity continuous training (MICT)
description: Exercise training on bicycle ergometer with moderate intensity (60 - 65 % of individual maximal power output)
arm group label: Moderate intensity continuous training
criteria: 
gender: Male
minimum age: 19 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ivo Volf, PhD
phone: +43 40160
phone ext: 31421
email: ivo.volf@meduniwien.ac.at
last name: Rochus Pokan, MD
phone: +43 4277 4887225
email: rochus.pokan@univie.ac.at
facility: 
status: Recruiting
contact: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Stefan Heber
investigator title: Dr.med.univ. Dr.rer.nat.
mesh term: Prediabetic State
sharing ipd: Undecided