<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/NCT03821558</url>
  </required_header>
  <id_info>
    <org_study_id>UKCLRehab0012019</org_study_id>
    <nct_id>NCT03821558</nct_id>
  </id_info>
  <brief_title>Exercise Training in Individuals With Coronary Artery Disease</brief_title>
  <acronym>ReKoBo</acronym>
  <official_title>Cardiovascular Rehabilitation in Coronary Artery Disease Patients: Influence of Different Types of Exercise Training on Selected Cardiovascular Parameters</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Centre Ljubljana</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this controlled trial, patients referred to post-myocardial infarction cardiac&#xD;
      rehabilitation will be randomized to either interval or continuous training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial would i) compare the acute effects of each exercise type on selected cardiovascular&#xD;
      indicators; ii) compare the chronic effects of each exercise type on selected cardiovascular&#xD;
      indicators; iii) provide information on the association between acute and chronic effects of&#xD;
      each exercise type; iv) provide insight into possible mechanisms of effectiveness of each&#xD;
      exercise type; v) identify the most safe and effective exercise type for patients with&#xD;
      coronary artery disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">August 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of flow-mediated dilatation of the brachial artery, measured in %</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of the arterial stiffness coefficient</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of maximal oxygen uptake during exercise, measured in ml/kg/min</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of the heart rate variability</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of the heart rate recovery</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in health-related quality of life using SF-36 questionnaire, measured in points</measure>
    <time_frame>3 months</time_frame>
    <description>It is a self-administered questionnaire comprising 36 items measuring eight dimensions and two subscales (physical and mental)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in IL-6, IL-8, IL-10, TNF-alpha and NT-proBNP levels, measured in ng/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in osteopontin and D-dimer levels, measured in microg/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in selectin and hsCRP, measured in mg/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hsTnI, CK MB, endocan, sST2, galectin-3, NGAL, CD40 ligand and BDNF, measured in ng/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in copeptin levels, measured in pmol/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MR-proADM and MR-proANP, measured in nmol/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in homoarginine, ADMA and SDMA levels, measured in micromol/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fibrinogen and Lp(a) levels, measured in mg/dl</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insuline level, measure in microIU/ml</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in total cholesterol, LDL, HDL, triglycerides and glucose levels, measured in mmol/l</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in overall haemostatic potential</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in the flow-mediated dilation during single exercise training session, measured in %</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in IL-6, IL-8, IL-10, TNF-alpha and NT-proBNP levels during single exercise training session, measured in ng/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in selectin and hsCRP during single exercise training session, measured in mg/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in hsTnI, CK MB, endocan, sST2, galectin-3, NGAL, CD40 ligand and BDNF levels during single exercise training session, measured in ng/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in copeptin levels during single exercise training session, measured in pmol/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in homoarginine, ADMA and SDMA levels during single exercise training session, measured in micromol/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in fibrinogen level during single exercise training session, measured in mg/dl</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in insuline levels during single exercise training session, measure in microIU/ml</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in osteopontin and D-dimer levels during single exercise training session, measured in microg/l</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in overall haemostatic potential during single exercise training session</measure>
    <time_frame>3 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">115</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Interval training group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients to be randomized to the 'interval training group' will have exercise training sessions 3 times per week for a period of 12 weeks. During training, they will undergo interval exercise series composed of high-intensity intervals (80-90% of peak exercise performance) and low-intensity intervals (60-70% of peak exercise performance).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous training group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients to be randomized to the 'continuous training group' will have exercise training sessions 3 times per week for a period of 12 weeks. During training, they will undergo moderate continuous exercise training at 75% of peak exercise performance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise training</intervention_name>
    <description>Patients to be randomized to the 'interval training group' or 'continuous training group' will undergo exercise training sessions with different intensity levels.</description>
    <arm_group_label>Continuous training group</arm_group_label>
    <arm_group_label>Interval training group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  myocardium infarction 120 days prior to cardiac rehabilitation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contraindications for exercise training,&#xD;
&#xD;
          -  uncontrolled dysrhythmias,&#xD;
&#xD;
          -  uncontrolled heart failure (New York Heart Association (NYHA) stage IV),&#xD;
&#xD;
          -  intellectual development disorder,&#xD;
&#xD;
          -  pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Borut Jug, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Centre Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Slovenia</country>
  </location_countries>
  <reference>
    <citation>Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun 19;115(24):3086-94. doi: 10.1161/CIRCULATIONAHA.106.675041. Epub 2007 Jun 4.</citation>
    <PMID>17548726</PMID>
  </reference>
  <reference>
    <citation>Liou K, Ho S, Fildes J, Ooi SY. High Intensity Interval versus Moderate Intensity Continuous Training in Patients with Coronary Artery Disease: A Meta-analysis of Physiological and Clinical Parameters. Heart Lung Circ. 2016 Feb;25(2):166-74. doi: 10.1016/j.hlc.2015.06.828. Epub 2015 Jul 22.</citation>
    <PMID>26375499</PMID>
  </reference>
  <reference>
    <citation>Conraads VM, Pattyn N, De Maeyer C, Beckers PJ, Coeckelberghs E, Cornelissen VA, Denollet J, Frederix G, Goetschalckx K, Hoymans VY, Possemiers N, Schepers D, Shivalkar B, Voigt JU, Van Craenenbroeck EM, Vanhees L. Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: the SAINTEX-CAD study. Int J Cardiol. 2015 Jan 20;179:203-10. doi: 10.1016/j.ijcard.2014.10.155. Epub 2014 Oct 25.</citation>
    <PMID>25464446</PMID>
  </reference>
  <reference>
    <citation>Villelabeitia-Jaureguizar K, Vicente-Campos D, Senen AB, Jimenez VH, Garrido-Lestache MEB, Chicharro JL. Effects of high-intensity interval versus continuous exercise training on post-exercise heart rate recovery in coronary heart-disease patients. Int J Cardiol. 2017 Oct 1;244:17-23. doi: 10.1016/j.ijcard.2017.06.067. Epub 2017 Jun 17.</citation>
    <PMID>28648356</PMID>
  </reference>
  <reference>
    <citation>Currie KD, Rosen LM, Millar PJ, McKelvie RS, MacDonald MJ. Heart rate recovery and heart rate variability are unchanged in patients with coronary artery disease following 12 weeks of high-intensity interval and moderate-intensity endurance exercise training. Appl Physiol Nutr Metab. 2013 Jun;38(6):644-50. doi: 10.1139/apnm-2012-0354. Epub 2013 Jan 17.</citation>
    <PMID>23724882</PMID>
  </reference>
  <reference>
    <citation>Novakovic M, Prokselj K, Rajkovic U, Vizintin Cuderman T, Jansa Trontelj K, Fras Z, Jug B. Exercise training in adults with repaired tetralogy of Fallot: A randomized controlled pilot study of continuous versus interval training. Int J Cardiol. 2018 Mar 15;255:37-44. doi: 10.1016/j.ijcard.2017.12.105. Epub 2018 Jan 3.</citation>
    <PMID>29338917</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 6, 2019</study_first_submitted>
  <study_first_submitted_qc>January 27, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>December 8, 2021</last_update_submitted>
  <last_update_submitted_qc>December 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Centre Ljubljana</investigator_affiliation>
    <investigator_full_name>Borut Jug</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>exercise</keyword>
  <keyword>interval training</keyword>
  <keyword>continuous training</keyword>
  <keyword>endothelial dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</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/NCT03821558
org study id: UKCLRehab0012019
nct id: NCT03821558
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In this controlled trial, patients referred to post-myocardial infarction cardiac
      rehabilitation will be randomized to either interval or continuous training.
The trial would i) compare the acute effects of each exercise type on selected cardiovascular
      indicators; ii) compare the chronic effects of each exercise type on selected cardiovascular
      indicators; iii) provide information on the association between acute and chronic effects of
      each exercise type; iv) provide insight into possible mechanisms of effectiveness of each
      exercise type; v) identify the most safe and effective exercise type for patients with
      coronary artery disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change of flow-mediated dilatation of the brachial artery, measured in %
time frame: 3 months
measure: Change of the arterial stiffness coefficient
time frame: 3 months
measure: Change of maximal oxygen uptake during exercise, measured in ml/kg/min
time frame: 3 months
measure: Change of the heart rate variability
time frame: 3 months
measure: Change of the heart rate recovery
time frame: 3 months
measure: Change in health-related quality of life using SF-36 questionnaire, measured in points
time frame: 3 months
description: It is a self-administered questionnaire comprising 36 items measuring eight dimensions and two subscales (physical and mental)
measure: Change in IL-6, IL-8, IL-10, TNF-alpha and NT-proBNP levels, measured in ng/l
time frame: 3 months
measure: Change in osteopontin and D-dimer levels, measured in microg/l
time frame: 3 months
measure: Change in selectin and hsCRP, measured in mg/l
time frame: 3 months
measure: Change in hsTnI, CK MB, endocan, sST2, galectin-3, NGAL, CD40 ligand and BDNF, measured in ng/l
time frame: 3 months
measure: Change in copeptin levels, measured in pmol/l
time frame: 3 months
measure: Change in MR-proADM and MR-proANP, measured in nmol/l
time frame: 3 months
measure: Change in homoarginine, ADMA and SDMA levels, measured in micromol/l
time frame: 3 months
measure: Change in fibrinogen and Lp(a) levels, measured in mg/dl
time frame: 3 months
measure: Change in insuline level, measure in microIU/ml
time frame: 3 months
measure: Change in total cholesterol, LDL, HDL, triglycerides and glucose levels, measured in mmol/l
time frame: 3 months
measure: Change in overall haemostatic potential
time frame: 3 months
measure: Change in the flow-mediated dilation during single exercise training session, measured in %
time frame: 3 months
measure: Change in IL-6, IL-8, IL-10, TNF-alpha and NT-proBNP levels during single exercise training session, measured in ng/l
time frame: 3 months
measure: Change in selectin and hsCRP during single exercise training session, measured in mg/l
time frame: 3 months
measure: Change in hsTnI, CK MB, endocan, sST2, galectin-3, NGAL, CD40 ligand and BDNF levels during single exercise training session, measured in ng/l
time frame: 3 months
measure: Change in copeptin levels during single exercise training session, measured in pmol/l
time frame: 3 months
measure: Change in homoarginine, ADMA and SDMA levels during single exercise training session, measured in micromol/l
time frame: 3 months
measure: Change in fibrinogen level during single exercise training session, measured in mg/dl
time frame: 3 months
measure: Change in insuline levels during single exercise training session, measure in microIU/ml
time frame: 3 months
measure: Change in osteopontin and D-dimer levels during single exercise training session, measured in microg/l
time frame: 3 months
measure: Change in overall haemostatic potential during single exercise training session
time frame: 3 months
arm group label: Interval training group
arm group type: Active Comparator
description: Patients to be randomized to the 'interval training group' will have exercise training sessions 3 times per week for a period of 12 weeks. During training, they will undergo interval exercise series composed of high-intensity intervals (80-90% of peak exercise performance) and low-intensity intervals (60-70% of peak exercise performance).
arm group label: Continuous training group
arm group type: Active Comparator
description: Patients to be randomized to the 'continuous training group' will have exercise training sessions 3 times per week for a period of 12 weeks. During training, they will undergo moderate continuous exercise training at 75% of peak exercise performance.
intervention type: Other
intervention name: Exercise training
description: Patients to be randomized to the 'interval training group' or 'continuous training group' will undergo exercise training sessions with different intensity levels.
arm group label: Continuous training group
arm group label: Interval training group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Borut Jug, MD, PhD
role: Principal Investigator
affiliation: University Medical Centre Ljubljana
facility: 
country: Slovenia
citation: Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun 19;115(24):3086-94. doi: 10.1161/CIRCULATIONAHA.106.675041. Epub 2007 Jun 4.
PMID: 17548726
citation: Liou K, Ho S, Fildes J, Ooi SY. High Intensity Interval versus Moderate Intensity Continuous Training in Patients with Coronary Artery Disease: A Meta-analysis of Physiological and Clinical Parameters. Heart Lung Circ. 2016 Feb;25(2):166-74. doi: 10.1016/j.hlc.2015.06.828. Epub 2015 Jul 22.
PMID: 26375499
citation: Conraads VM, Pattyn N, De Maeyer C, Beckers PJ, Coeckelberghs E, Cornelissen VA, Denollet J, Frederix G, Goetschalckx K, Hoymans VY, Possemiers N, Schepers D, Shivalkar B, Voigt JU, Van Craenenbroeck EM, Vanhees L. Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: the SAINTEX-CAD study. Int J Cardiol. 2015 Jan 20;179:203-10. doi: 10.1016/j.ijcard.2014.10.155. Epub 2014 Oct 25.
PMID: 25464446
citation: Villelabeitia-Jaureguizar K, Vicente-Campos D, Senen AB, Jimenez VH, Garrido-Lestache MEB, Chicharro JL. Effects of high-intensity interval versus continuous exercise training on post-exercise heart rate recovery in coronary heart-disease patients. Int J Cardiol. 2017 Oct 1;244:17-23. doi: 10.1016/j.ijcard.2017.06.067. Epub 2017 Jun 17.
PMID: 28648356
citation: Currie KD, Rosen LM, Millar PJ, McKelvie RS, MacDonald MJ. Heart rate recovery and heart rate variability are unchanged in patients with coronary artery disease following 12 weeks of high-intensity interval and moderate-intensity endurance exercise training. Appl Physiol Nutr Metab. 2013 Jun;38(6):644-50. doi: 10.1139/apnm-2012-0354. Epub 2013 Jan 17.
PMID: 23724882
citation: Novakovic M, Prokselj K, Rajkovic U, Vizintin Cuderman T, Jansa Trontelj K, Fras Z, Jug B. Exercise training in adults with repaired tetralogy of Fallot: A randomized controlled pilot study of continuous versus interval training. Int J Cardiol. 2018 Mar 15;255:37-44. doi: 10.1016/j.ijcard.2017.12.105. Epub 2018 Jan 3.
PMID: 29338917
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Borut Jug
investigator title: Associate Professor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Myocardial Infarction
mesh term: Infarction
sharing ipd: No