<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/NCT02261168</url>
  </required_header>
  <id_info>
    <org_study_id>METC143027</org_study_id>
    <secondary_id>NL49363.068.14</secondary_id>
    <nct_id>NCT02261168</nct_id>
  </id_info>
  <brief_title>Day-Night Rhythm in Human Skeletal Muscle</brief_title>
  <official_title>Day-night Rhythm in Human Skeletal Muscle Metabolism</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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism&#xD;
      in healthy lean subjects. Subjects will stay at the research facility for 44 hours with a&#xD;
      standardized living protocol during which several measurements of skeletal muscle and whole&#xD;
      body energy metabolism will be performed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent evidence from both observational and experimental studies indicates that disobeying&#xD;
      our normal day-night rhythm negatively influences our metabolic and cardiovascular health,&#xD;
      possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of&#xD;
      obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent&#xD;
      research indicates that also skeletal muscle mitochondrial function under the influence of a&#xD;
      day-night rhythm. The main objective of this study is to investigate the presence of a&#xD;
      day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function)&#xD;
      of healthy young participants. Therefore, subjects will stay at the research unit for 44&#xD;
      hours, with standardized meals and sleeping time. During this period we will take five muscle&#xD;
      biopsies, perform indirect calorimetry measurements and blood draws.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Day-night rhythm in skeletal muscle mitochondrial respiration</measure>
    <time_frame>40 hours.</time_frame>
    <description>O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Day-night rhythm in whole-body energy metabolism</measure>
    <time_frame>40 hours.</time_frame>
    <description>Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.</measure>
    <time_frame>40 hours.</time_frame>
    <description>Quantify mRNA and protein levels by qPCR or micro-array and Western blots</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)</measure>
    <time_frame>measured during the 2nd study day</time_frame>
    <description>Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)</measure>
    <time_frame>measured during the 2nd study day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's</measure>
    <time_frame>measured during the 2nd study day</time_frame>
    <description>Measured by qPCR and Western Blots</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver volume and liver lipid concentration during the day</measure>
    <time_frame>First study day 6 PM, second study day 7 AM</time_frame>
    <description>Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Standardized living protocol</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standardized living protocol</intervention_name>
    <description>Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.</description>
    <arm_group_label>Standardized living protocol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Caucasian&#xD;
&#xD;
          -  Healthy (as determined by dependent physician based on medical questionnaire)&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Age: 18-35 years&#xD;
&#xD;
          -  Normal BMI (18-25 kg/m2)&#xD;
&#xD;
          -  Regular sleeping time (normally 7-9h daily)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)&#xD;
&#xD;
          -  Heavily varying sleep-wake rhythm&#xD;
&#xD;
          -  Shiftwork during last 3 months&#xD;
&#xD;
          -  Travel across &gt;1 time zone in the last 3 months&#xD;
&#xD;
          -  Engagement in exercise &gt; 2 hours total per week&#xD;
&#xD;
          -  Using &gt;400mg caffeine daily&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Unstable body weight (weight gain or loss &gt; 3kg in the last 3 months)&#xD;
&#xD;
          -  Significant food allergies/intolerance (seriously hampering study meals)&#xD;
&#xD;
          -  Participation in another biomedical study within 1 month before the first study visit&#xD;
&#xD;
          -  Any contra-indication to Magnetic Resonance Imaging (MRI) scanning&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Schrauwen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>September 4, 2015</last_update_submitted>
  <last_update_submitted_qc>September 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 7, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Circadian Rhythm</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <!-- 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/NCT02261168
org study id: METC143027
secondary id: NL49363.068.14
nct id: NCT02261168
lead sponsor: 
has dmc: No
This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism
      in healthy lean subjects. Subjects will stay at the research facility for 44 hours with a
      standardized living protocol during which several measurements of skeletal muscle and whole
      body energy metabolism will be performed.
Recent evidence from both observational and experimental studies indicates that disobeying
      our normal day-night rhythm negatively influences our metabolic and cardiovascular health,
      possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of
      obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent
      research indicates that also skeletal muscle mitochondrial function under the influence of a
      day-night rhythm. The main objective of this study is to investigate the presence of a
      day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function)
      of healthy young participants. Therefore, subjects will stay at the research unit for 44
      hours, with standardized meals and sleeping time. During this period we will take five muscle
      biopsies, perform indirect calorimetry measurements and blood draws.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Day-night rhythm in skeletal muscle mitochondrial respiration
time frame: 40 hours.
description: O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates
measure: Day-night rhythm in whole-body energy metabolism
time frame: 40 hours.
description: Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry
measure: Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.
time frame: 40 hours.
description: Quantify mRNA and protein levels by qPCR or micro-array and Western blots
measure: Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)
time frame: measured during the 2nd study day
description: Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.
measure: Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)
time frame: measured during the 2nd study day
measure: Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's
time frame: measured during the 2nd study day
description: Measured by qPCR and Western Blots
measure: Change in liver volume and liver lipid concentration during the day
time frame: First study day 6 PM, second study day 7 AM
description: Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)
arm group label: Standardized living protocol
arm group type: Other
description: Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry.
intervention type: Other
intervention name: Standardized living protocol
description: Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.
arm group label: Standardized living protocol
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Patrick Schrauwen, PhD
role: Principal Investigator
affiliation: Professor
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance