xml: <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/NCT06014684</url>
    </required_header>
    <id_info>
      <org_study_id>NL83421.068.22</org_study_id>
      <nct_id>NCT06014684</nct_id>
    </id_info>
    <brief_title>Timing Exercise Training as Strategy to Improve Insulin Sensitivity and Substrate Metabolism in Men and Woman With Pre-diabetes</brief_title>
    <acronym>Timed Training</acronym>
    <official_title>Timing Exercise Training as Strategy to Improve Insulin Sensitivity and Substrate Metabolism in Men and Woman With Pre-diabetes</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Maastricht University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Maastricht University Medical Center</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>
        n a retrospective analysis of an exercise training program performed either in the morning or&#xD;
        afternoon, we found that the afternoon training group improved their peripheral insulin&#xD;
        sensitivity and fasting plasma glucose levels to a greater extent than the morning group.&#xD;
        However, underlying mechanisms are unclear.&#xD;
  &#xD;
        The main objective of this study is to determine whether prolonged exercise training in the&#xD;
        afternoon (15:00-17:00 PM) differs from exercise training in the morning (07:00-09:00 AM) in&#xD;
        improving insulin sensitivity in individuals with pre-diabetes, and to investigate its&#xD;
        underlying mechanisms.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Rationale: Various metabolic processes, including resting metabolic rate, insulin sensitivity&#xD;
        and insulin secretion, follow a recurring 24-hour cycle. These rhythms are shown to be&#xD;
        disturbed in in pre-diabetes volunteers compared to young healthy volunteers. In a&#xD;
        retrospective analysis of an exercise training program performed either in the morning or&#xD;
        afternoon, we found that the afternoon training group improved their peripheral insulin&#xD;
        sensitivity and fasting plasma glucose levels to a greater extent than the morning group.&#xD;
        However, underlying mechanisms are unclear.&#xD;
  &#xD;
        Objective: The main objective of this study is to determine whether prolonged exercise&#xD;
        training in the afternoon (15:00-17:00 PM) differs from exercise training in the morning&#xD;
        (07:00-09:00 AM) in improving insulin sensitivity in individuals with pre-diabetes, and to&#xD;
        investigate its underlying mechanisms.&#xD;
  &#xD;
        Study design: The present study is a randomized double arm longitudinal intervention study in&#xD;
        a pre and post design.&#xD;
  &#xD;
        Study population: 24 pre-diabetic individuals (men and postmenopausal women aged 40 - 75&#xD;
        years and with BMI ≥ 25 and ≤ 38 kg/m2) will complete this study (12 participants in the&#xD;
        morning training group and 12 participants in the afternoon training group). From experience&#xD;
        with similar studies, we estimate a drop-out rate of 20% and a screening failure of 70%&#xD;
        (because individuals often do not know they are pre-diabetic). This results in maximally 30&#xD;
        participants that have to be included and 100 participants that have to be screened&#xD;
        (maximally).&#xD;
  &#xD;
        Intervention (if applicable): Participants will perform a 12-weeks supervised high intensity&#xD;
        interval training (HIIT) program with three ~30 min exercise sessions per week. Participants&#xD;
        will be randomly assigned to the morning or afternoon training time. To assess the outcomes,&#xD;
        participants will come to the university for a 43h measurement period both before and after&#xD;
        the 12-week training program.&#xD;
  &#xD;
        Main study parameters/endpoints: The primary study endpoint is peripheral insulin sensitivity&#xD;
        measured via a 2-step hyperinsulinemic-euglycemic clamp. The secondary outcomes are 24h&#xD;
        energy and substrate metabolism. Exploratory outcomes are body composition, intrahepatic&#xD;
        lipid content and composition, hepatic insulin sensitivity, hepatic glycogen levels, maximal&#xD;
        aerobic capacity, skeletal muscle oxidative capacity, visceral and subcutaneous adipose&#xD;
        tissue volume, sleeping metabolic rate, blood glucose levels (continuously measured over&#xD;
        7days) and immune responses.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 13, 2023</start_date>
    <completion_date type="Anticipated">March 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 1, 2026</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>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Peripheral Insulin sensitivity</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>Glucose disposal rate under high insulin concentrations during the second step of the 2-step hyperinsulinemic-euglycemic clamp.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>24h whole body energy expenditure</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>energy expenditure as measured by a 24h stay in the respiration chamber</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>24h substrate metabolism</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>24h substrate metabolism as measured by a 24h stay in the respiration chamber</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Body composition by Dual Energy X-ray Absorptiometry (DEXA)</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>fat-free mass (kg and percentage)</description>
    </other_outcome>
    <other_outcome>
      <measure>Body composition by Dual Energy X-ray Absorptiometry (DEXA)</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>fat mass (kg and percentage)</description>
    </other_outcome>
    <other_outcome>
      <measure>Intrahepatic lipid content and composition</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Hepatic glycogen levels</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>VO2 max cycling test</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>measurement of participants' maximal aerobic capacity, absolute (L/min) and relative (ml/min/kg)</description>
    </other_outcome>
    <other_outcome>
      <measure>Skeletal muscle oxidative capacity</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
      <description>Ex vivo high-resolution respirometry using a two chamber Oxygraph (OROBOROS Instruments) will be performed. Multiple substrate/inhibitor titration protocols will be applied to extensively characterize the mitochondrial capacity of skeletal muscle fibers</description>
    </other_outcome>
    <other_outcome>
      <measure>Sleeping metabolic rate</measure>
      <time_frame>measured before and after the 12 weeks training program</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Blood glucose levels measured continuously over 7 days.</measure>
      <time_frame>measured before and at the end the 12 weeks training program</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Pre-diabetes</condition>
    <condition>Overweight and Obesity</condition>
    <arm_group>
      <arm_group_label>AM exercise</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HIIT program performed between 07:00-09:00 AM</description>
    </arm_group>
    <arm_group>
      <arm_group_label>PM exercise</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HIIT program performed between 15:00-17:00 PM</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Timing of exercise</intervention_name>
      <description>High Intensity Interval Training (HIIT) program for 12 weeks (3 per week/36 sessions in total)</description>
      <arm_group_label>AM exercise</arm_group_label>
      <arm_group_label>PM exercise</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 40-75 years.&#xD;
  &#xD;
            -  Body mass index (BMI) ≥25 kg/m2&#xD;
  &#xD;
            -  Male, or postmenopausal (at least 1 year post cessation of menses) female&#xD;
  &#xD;
            -  Pre-diabetes based on one or a combination of the following criteria:&#xD;
  &#xD;
                 -  Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1&#xD;
                    mmol/l 120 minutes after glucose drink consumption during OGTT in screening&#xD;
  &#xD;
                 -  ImpairedFastingGlucose(IFG):Fastingplasmaglucose≥6.1mmol/land≤6.9 mmol/l&#xD;
  &#xD;
                 -  Insulin Resistance: glucose clearance rate ≤ 360 mL/kg/min, as determined during&#xD;
                    the OGTT using OGIS120.&#xD;
  &#xD;
                 -  HbA1cof5.7-6.4%&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Type 2 diabetes&#xD;
  &#xD;
            -  Patients with active congestive heart failure and and/or severe renal and or liver&#xD;
               insufficiency&#xD;
  &#xD;
            -  Uncontrolled hypertension&#xD;
  &#xD;
            -  Any contra-indication for MRI scanning&#xD;
  &#xD;
            -  Alcohol consumption of &gt;3 servings per day for man and &gt;2 servings per day for woman&#xD;
  &#xD;
            -  Smoking&#xD;
  &#xD;
            -  Unstable body weight (weight gain or loss &gt; 5kg in the last 3 months)&#xD;
  &#xD;
            -  Previous enrolment in a clinical study with an investigational product during the last&#xD;
               3 months or as judged by the Investigator which would possibly hamper our study&#xD;
               results.&#xD;
  &#xD;
            -  Medication use known to hamper subject's safety during the study procedures.&#xD;
  &#xD;
            -  Subjects who do not want to be informed about unexpected medical findings.&#xD;
  &#xD;
            -  Men: Hb &lt;8.0 mmol/L, Women: Hb &lt;7.0 mmol/l&#xD;
  &#xD;
            -  Heavily varying sleep-wake rhythm (i.e. night shift work and travels across time&#xD;
               zones).&#xD;
  &#xD;
            -  Significant food allergies/intolerance (seriously hampering study meals)&#xD;
  &#xD;
            -  Blood donation during or within 2 months prior to the study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Ivo Habets, MSc</last_name>
      <phone>+31 88 388 7287</phone>
      <email>i.habets@maastrichtuniversity.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Soraya de Kam, MSc</last_name>
      <email>soraya.dekam@maastrichtuniversity.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Maastricht University</name>
        <address>
          <city>Maastricht</city>
          <state>Limburg</state>
          <zip>6229 ER</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ivo Habets, MSc</last_name>
        <phone>+31 88 388 7287</phone>
        <email>i.habets@maastrichtuniversity.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</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>Diabetes Mellitus</mesh_term>
      <mesh_term>Overweight</mesh_term>
      <mesh_term>Insulin Resistance</mesh_term>
      <mesh_term>Prediabetic State</mesh_term>
      <mesh_term>Glucose Intolerance</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06014684
  org study id: NL83421.068.22
  nct id: NCT06014684
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  n a retrospective analysis of an exercise training program performed either in the morning or
        afternoon, we found that the afternoon training group improved their peripheral insulin
        sensitivity and fasting plasma glucose levels to a greater extent than the morning group.
        However, underlying mechanisms are unclear.
  
        The main objective of this study is to determine whether prolonged exercise training in the
        afternoon (15:00-17:00 PM) differs from exercise training in the morning (07:00-09:00 AM) in
        improving insulin sensitivity in individuals with pre-diabetes, and to investigate its
        underlying mechanisms.
  Rationale: Various metabolic processes, including resting metabolic rate, insulin sensitivity
        and insulin secretion, follow a recurring 24-hour cycle. These rhythms are shown to be
        disturbed in in pre-diabetes volunteers compared to young healthy volunteers. In a
        retrospective analysis of an exercise training program performed either in the morning or
        afternoon, we found that the afternoon training group improved their peripheral insulin
        sensitivity and fasting plasma glucose levels to a greater extent than the morning group.
        However, underlying mechanisms are unclear.
  
        Objective: The main objective of this study is to determine whether prolonged exercise
        training in the afternoon (15:00-17:00 PM) differs from exercise training in the morning
        (07:00-09:00 AM) in improving insulin sensitivity in individuals with pre-diabetes, and to
        investigate its underlying mechanisms.
  
        Study design: The present study is a randomized double arm longitudinal intervention study in
        a pre and post design.
  
        Study population: 24 pre-diabetic individuals (men and postmenopausal women aged 40 - 75
        years and with BMI ≥ 25 and ≤ 38 kg/m2) will complete this study (12 participants in the
        morning training group and 12 participants in the afternoon training group). From experience
        with similar studies, we estimate a drop-out rate of 20% and a screening failure of 70%
        (because individuals often do not know they are pre-diabetic). This results in maximally 30
        participants that have to be included and 100 participants that have to be screened
        (maximally).
  
        Intervention (if applicable): Participants will perform a 12-weeks supervised high intensity
        interval training (HIIT) program with three ~30 min exercise sessions per week. Participants
        will be randomly assigned to the morning or afternoon training time. To assess the outcomes,
        participants will come to the university for a 43h measurement period both before and after
        the 12-week training program.
  
        Main study parameters/endpoints: The primary study endpoint is peripheral insulin sensitivity
        measured via a 2-step hyperinsulinemic-euglycemic clamp. The secondary outcomes are 24h
        energy and substrate metabolism. Exploratory outcomes are body composition, intrahepatic
        lipid content and composition, hepatic insulin sensitivity, hepatic glycogen levels, maximal
        aerobic capacity, skeletal muscle oxidative capacity, visceral and subcutaneous adipose
        tissue volume, sleeping metabolic rate, blood glucose levels (continuously measured over
        7days) and immune responses.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Peripheral Insulin sensitivity
  time frame: measured before and after the 12 weeks training program
  description: Glucose disposal rate under high insulin concentrations during the second step of the 2-step hyperinsulinemic-euglycemic clamp.
  measure: 24h whole body energy expenditure
  time frame: measured before and after the 12 weeks training program
  description: energy expenditure as measured by a 24h stay in the respiration chamber
  measure: 24h substrate metabolism
  time frame: measured before and after the 12 weeks training program
  description: 24h substrate metabolism as measured by a 24h stay in the respiration chamber
  measure: Body composition by Dual Energy X-ray Absorptiometry (DEXA)
  time frame: measured before and after the 12 weeks training program
  description: fat-free mass (kg and percentage)
  measure: Body composition by Dual Energy X-ray Absorptiometry (DEXA)
  time frame: measured before and after the 12 weeks training program
  description: fat mass (kg and percentage)
  measure: Intrahepatic lipid content and composition
  time frame: measured before and after the 12 weeks training program
  measure: Hepatic glycogen levels
  time frame: measured before and after the 12 weeks training program
  measure: VO2 max cycling test
  time frame: measured before and after the 12 weeks training program
  description: measurement of participants' maximal aerobic capacity, absolute (L/min) and relative (ml/min/kg)
  measure: Skeletal muscle oxidative capacity
  time frame: measured before and after the 12 weeks training program
  description: Ex vivo high-resolution respirometry using a two chamber Oxygraph (OROBOROS Instruments) will be performed. Multiple substrate/inhibitor titration protocols will be applied to extensively characterize the mitochondrial capacity of skeletal muscle fibers
  measure: Sleeping metabolic rate
  time frame: measured before and after the 12 weeks training program
  measure: Blood glucose levels measured continuously over 7 days.
  time frame: measured before and at the end the 12 weeks training program
  arm group label: AM exercise
  arm group type: Experimental
  description: HIIT program performed between 07:00-09:00 AM
  arm group label: PM exercise
  arm group type: Experimental
  description: HIIT program performed between 15:00-17:00 PM
  intervention type: Behavioral
  intervention name: Timing of exercise
  description: High Intensity Interval Training (HIIT) program for 12 weeks (3 per week/36 sessions in total)
  arm group label: AM exercise
  arm group label: PM exercise
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 75 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Ivo Habets, MSc
  phone: +31 88 388 7287
  email: i.habets@maastrichtuniversity.nl
  last name: Soraya de Kam, MSc
  email: soraya.dekam@maastrichtuniversity.nl
  facility: 
  status: Recruiting
  contact: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: Diabetes Mellitus
  mesh term: Overweight
  mesh term: Insulin Resistance
  mesh term: Prediabetic State
  mesh term: Glucose Intolerance