<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/NCT03276442</url>
  </required_header>
  <id_info>
    <org_study_id>CircHFJC2017</org_study_id>
    <nct_id>NCT03276442</nct_id>
  </id_info>
  <brief_title>Biorhythms in Metabolic Tissues</brief_title>
  <official_title>Biological Rhythms in Metabolic Tissues: Impact of Diet</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Swedish Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala University</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>
      Metabolism is increasingly recognized as being highly regulated by anticipatory biological&#xD;
      rhythms (circadian rhythms or &quot;biorhythms&quot;), which are driven by molecular feedback loops,&#xD;
      and which are approximately 24 hours long (&quot;circa diem&quot;). These circadian rhythms exist both&#xD;
      centrally, in the brain, but also in the periphery, and are specific to many tissues&#xD;
      depending on their main biological function or functions. Whereas these circadian rhythms&#xD;
      have been thoroughly characterized in other organisms, their role in humans remain poorly&#xD;
      understood, partly because of the difficulty in studying these rhythms in peripheral tissues.&#xD;
      The investigators therefore aim to characterize these rhythms in primarily skeletal muscle&#xD;
      and adipose tissue in healthy young volunteers (using the so-called constant routine&#xD;
      paradigm), and how these rhythms interact with one another at various genetic and molecular&#xD;
      levels. At the same time, the investigators aim to study how an unhealthy vs. healthy diet&#xD;
      can alter these circadian rhythms, and how they interact with circadian rhythms in other&#xD;
      tissue compartments such as those expressed by blood cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2019</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>
    <intervention_model_description>Participants will be studied in a crossover design both after a &quot;healthy diet&quot;, and after an &quot;unhealthy diet&quot;</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>In the crossover subgroup condition, participants will not be briefed about what diet they will receive before the actual onset of the dietary intervention</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in clock gene &amp; associated omic circadian rhythms</measure>
    <time_frame>Measured repeatedly (every 6 hours for 24 hours) during a period of extended wakefulness, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Changes in clock gene &amp; associated clock-regulated &amp; clock-independent metabolic and omic circadian rhythms (e.g. in epigenome, transcriptome, metabolites) in peripheral tissues (primarily skeletal muscle and adipose tissue), and interplay between these rhythms across the 24-h period and under the different dietary conditions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Wakefulness-induced changes and subsequent recovery at omic levels</measure>
    <time_frame>Following each dietary intervention (i.e. over a total period of 6-7 weeks), measured repeatedly (every 2-6 hours for 24 hours) during a period of extended wakefulness, and after recovery sleep</time_frame>
    <description>Changes at omic levels (e.g. DNA methylation, transcriptome, proteome, metabolome) in peripheral tissues (primarily skeletal muscle and adipose tissue), urine and feces samples due to extended wakefulness following subsequent recovery, following each dietary intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-h rhythms in blood</measure>
    <time_frame>Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Changes in rhythms in blood-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diet-induced changes in gut microbiota and relation to circadian rhythms</measure>
    <time_frame>Measured throughout study participation, i.e. on average over 6-7 weeks</time_frame>
    <description>Changes in gut microbiota (metagenomic, compositional) due to dietary intervention, and relation to circadian rhythms measured across 24 hrs in peripheral tissues following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Energy expenditure rhythms</measure>
    <time_frame>Measured repeatedly (every 2 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Changes in energy expenditure rhythms due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine metabolite rhythms</measure>
    <time_frame>Measured throughout study participation, i.e. on average over 6-7 weeks</time_frame>
    <description>Changes in levels of urine metabolites due to dietary intervention, and relation to circadian rhythms across 24 hrs in peripheral tissues following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rhythms of blood markers of damage to the central nervous system</measure>
    <time_frame>Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Assessment of rhythms in of blood markers of damage to the central nervous system (e.g. Olink Proseek multiplex panel, neuron-specific enolase, S-100b) across a 24-h period and following subsequent recovery sleep, following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-h rhythms in saliva</measure>
    <time_frame>Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Changes in rhythms in saliva-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central circadian rhythms</measure>
    <time_frame>Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)</time_frame>
    <description>Changes in centrally driven circadian rhythms (e.g. temperature and melatonin), due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Sleep Deprivation</condition>
  <condition>Metabolic Disturbance</condition>
  <condition>Biological Clocks</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Healthy diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>'Low-fat dietary intervention' to be administered to participants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unhealthy diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>'High-fat dietary intervention' to be administered to participants</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low-fat dietary intervention</intervention_name>
    <description>Low-fat diet (5-7 days) preceding extended wakefulness under standardized conditions</description>
    <arm_group_label>Healthy diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High-fat dietary intervention</intervention_name>
    <description>High-fat diet (5-7 days) preceding extended wakefulness under standardized conditions</description>
    <arm_group_label>Unhealthy diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-33 yr&#xD;
&#xD;
          -  Healthy (self-reported) and not on medication&#xD;
&#xD;
          -  BMI 18-28 kg/m2 (and waist circumference &lt;102 cm), and weight stable (±5% body weight&#xD;
             in past 6 months)&#xD;
&#xD;
          -  Non-smoker and non-nicotine user&#xD;
&#xD;
          -  Regular sleep-wake pattern, with sleep duration of 7-9.25 hrs per night&#xD;
&#xD;
          -  Sedentary to moderately active with regular exercise habits the last 2 months&#xD;
&#xD;
          -  Regular daily meal pattern with 3 main meals&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major or chronic illness, e.g. diabetes, renal disease or inflammatory bowel disease&#xD;
&#xD;
          -  Current or history of endocrine or metabolic disorders&#xD;
&#xD;
          -  Psychiatric or neurological disorders (e.g. bipolar disorder, epilepsy)&#xD;
&#xD;
          -  Frequent gastrointestinal symptoms&#xD;
&#xD;
          -  Chronic medication&#xD;
&#xD;
          -  Any sleep disorder (e.g. irregular bedtimes, symptoms of insomnia)&#xD;
&#xD;
          -  Any issues with or allergies against the provided food items or utilized anesthesia&#xD;
&#xD;
          -  Shift work in the preceding three months or for a long duration&#xD;
&#xD;
          -  Time travel over two time zones in the preceding month&#xD;
&#xD;
          -  Too much weight gain or weight loss in the preceding 6 months&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>32 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Cedernaes</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jonathan Cedernaes, M.D., Ph.D.</last_name>
    <phone>0184714136</phone>
    <email>jonathan.cedernaes@neuro.uu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christian Benedict, Ph.D.</last_name>
    <phone>0184714136</phone>
    <email>christian.benedict@neuro.uu.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Neuroscience, Uppsala University</name>
      <address>
        <city>Uppsala</city>
        <zip>75324</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan Cedernaes, MD, PhD</last_name>
      <phone>+46184714102</phone>
      <email>jonathan.cedernaes@neuro.uu.se</email>
    </contact>
    <contact_backup>
      <last_name>Christian Benedict, PhD</last_name>
      <phone>46184714136</phone>
      <email>christian.benedict@neuro.uu.se</email>
    </contact_backup>
    <investigator>
      <last_name>Jonathan Cedernaes, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>October 10, 2017</last_update_submitted>
  <last_update_submitted_qc>October 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2017</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>Sleep Deprivation</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/NCT03276442
org study id: CircHFJC2017
nct id: NCT03276442
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Metabolism is increasingly recognized as being highly regulated by anticipatory biological
      rhythms (circadian rhythms or "biorhythms"), which are driven by molecular feedback loops,
      and which are approximately 24 hours long ("circa diem"). These circadian rhythms exist both
      centrally, in the brain, but also in the periphery, and are specific to many tissues
      depending on their main biological function or functions. Whereas these circadian rhythms
      have been thoroughly characterized in other organisms, their role in humans remain poorly
      understood, partly because of the difficulty in studying these rhythms in peripheral tissues.
      The investigators therefore aim to characterize these rhythms in primarily skeletal muscle
      and adipose tissue in healthy young volunteers (using the so-called constant routine
      paradigm), and how these rhythms interact with one another at various genetic and molecular
      levels. At the same time, the investigators aim to study how an unhealthy vs. healthy diet
      can alter these circadian rhythms, and how they interact with circadian rhythms in other
      tissue compartments such as those expressed by blood cells.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Participants will be studied in a crossover design both after a "healthy diet", and after an "unhealthy diet"
primary purpose: Basic Science
masking: None (Open Label)
masking description: In the crossover subgroup condition, participants will not be briefed about what diet they will receive before the actual onset of the dietary intervention
measure: Changes in clock gene & associated omic circadian rhythms
time frame: Measured repeatedly (every 6 hours for 24 hours) during a period of extended wakefulness, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Changes in clock gene & associated clock-regulated & clock-independent metabolic and omic circadian rhythms (e.g. in epigenome, transcriptome, metabolites) in peripheral tissues (primarily skeletal muscle and adipose tissue), and interplay between these rhythms across the 24-h period and under the different dietary conditions
measure: Wakefulness-induced changes and subsequent recovery at omic levels
time frame: Following each dietary intervention (i.e. over a total period of 6-7 weeks), measured repeatedly (every 2-6 hours for 24 hours) during a period of extended wakefulness, and after recovery sleep
description: Changes at omic levels (e.g. DNA methylation, transcriptome, proteome, metabolome) in peripheral tissues (primarily skeletal muscle and adipose tissue), urine and feces samples due to extended wakefulness following subsequent recovery, following each dietary intervention
measure: 24-h rhythms in blood
time frame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Changes in rhythms in blood-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
measure: Diet-induced changes in gut microbiota and relation to circadian rhythms
time frame: Measured throughout study participation, i.e. on average over 6-7 weeks
description: Changes in gut microbiota (metagenomic, compositional) due to dietary intervention, and relation to circadian rhythms measured across 24 hrs in peripheral tissues following the two dietary conditions
measure: Energy expenditure rhythms
time frame: Measured repeatedly (every 2 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Changes in energy expenditure rhythms due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
measure: Urine metabolite rhythms
time frame: Measured throughout study participation, i.e. on average over 6-7 weeks
description: Changes in levels of urine metabolites due to dietary intervention, and relation to circadian rhythms across 24 hrs in peripheral tissues following the two dietary conditions
measure: Rhythms of blood markers of damage to the central nervous system
time frame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Assessment of rhythms in of blood markers of damage to the central nervous system (e.g. Olink Proseek multiplex panel, neuron-specific enolase, S-100b) across a 24-h period and following subsequent recovery sleep, following the two dietary conditions
measure: 24-h rhythms in saliva
time frame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Changes in rhythms in saliva-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
measure: Central circadian rhythms
time frame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
description: Changes in centrally driven circadian rhythms (e.g. temperature and melatonin), due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
arm group label: Healthy diet
arm group type: Experimental
description: 'Low-fat dietary intervention' to be administered to participants
arm group label: Unhealthy diet
arm group type: Experimental
description: 'High-fat dietary intervention' to be administered to participants
intervention type: Other
intervention name: Low-fat dietary intervention
description: Low-fat diet (5-7 days) preceding extended wakefulness under standardized conditions
arm group label: Healthy diet
intervention type: Other
intervention name: High-fat dietary intervention
description: High-fat diet (5-7 days) preceding extended wakefulness under standardized conditions
arm group label: Unhealthy diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 32 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jonathan Cedernaes
role: Principal Investigator
affiliation: Uppsala University
last name: Jonathan Cedernaes, M.D., Ph.D.
phone: 0184714136
email: jonathan.cedernaes@neuro.uu.se
last name: Christian Benedict, Ph.D.
phone: 0184714136
email: christian.benedict@neuro.uu.se
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Sweden
responsible party type: Sponsor
mesh term: Sleep Deprivation
sharing ipd: No