<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/NCT03036592</url>
  </required_header>
  <id_info>
    <org_study_id>2017ES00001</org_study_id>
    <nct_id>NCT03036592</nct_id>
  </id_info>
  <brief_title>MTNR1B SNP*Food Timing Interaction on Glucose Control</brief_title>
  <acronym>ONTIME-MT</acronym>
  <official_title>MTNR1B SNP*Food Timing Interaction on Glucose Control in a Late Eater Mediterranean Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad de Murcia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidad de Murcia</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>
      The purpose of this investigation is to assess the role of melatonin receptor 1B (MTNR1B)&#xD;
      single nucleotide polymorphism (SNP)*food timing interaction on glucose control in the&#xD;
      deleterious effect in a vulnerable population with regular exposure to concurrent high&#xD;
      melatonin and food intake as late night eaters (those having dinner within 2.5 h before their&#xD;
      usual bed time). With the results from this study, we expect to advance our understanding of&#xD;
      the role of endogenous melatonin on glucose metabolism in late night eaters and carriers of&#xD;
      the MTNR1B risk allele, with potential implications on the guidelines to mitigate risk of&#xD;
      type 2 diabetes in late night eaters and carriers of the MTNR1B risk allele.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Late-night dinner eating is associated with increased risk for type-2-diabetes. The&#xD;
      underlying mechanism is unclear. One explanatory hypothesis is that the concurrence of&#xD;
      elevated circulating melatonin and high glucose concentrations (characterizing late-eating)&#xD;
      leads to impaired glucose-tolerance. However, to date, no study has tested the influence of&#xD;
      physiological melatonin concentrations on glucose tolerance. The discovery of melatonin&#xD;
      receptor MTNR1B as a diabetes risk gene provides evidence for a role of physiological levels&#xD;
      of melatonin in glucose control.&#xD;
&#xD;
      The aim of the current study is to test the hypothesis that the concurrence of meal timing&#xD;
      with elevated endogenous melatonin concentrations results in impaired glucose control and&#xD;
      that this effect is stronger in homozygous MTNR1B risk carriers than in non-carriers. To do&#xD;
      so we will test glucose tolerance using identical mixed meals under two glucose oral&#xD;
      tolerance test (OGTT) conditions: a) delayed OGTT or Late Eating (LE): starting1 hour before&#xD;
      their usual bed time, b) advanced OGTT or Early Eating (EE): starting 4 hours before habitual&#xD;
      bed time, in a randomized, cross-over study design.&#xD;
&#xD;
      These findings could support a clinical application for the screening of this SNP and the&#xD;
      possibility of implementing tailored and cost-effective behavioral interventions to prevent&#xD;
      type 2 diabetes in vulnerable populations.&#xD;
&#xD;
      These goals will be achieved through a specific approach:&#xD;
&#xD;
      • Interventional (randomized, cross-over controlled trials) (Aim 1): To study the potential&#xD;
      interaction between meal timing (dinner) and genetic variants MTNR1B for glucose tolerance in&#xD;
      obese women (n=1000).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 31, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve (AUC) glucose</measure>
    <time_frame>between 0-120 minutes, Visit 2 and 3</time_frame>
    <description>Investigators will measure insulin and glucose levels for 120 minutes at day time and night time visits, and compare them by genotype at selected loci.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disposition index</measure>
    <time_frame>between 0-120 minutes, Visit 2 and 3</time_frame>
    <description>Disposition index will be determined by frequently sampled oral glucose tolerance test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Corrected Insulin Response</measure>
    <time_frame>between 0-120 minutes, Visit 2 and 3</time_frame>
    <description>Corrected Insulin Response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin Sensitivity Index</measure>
    <time_frame>between 0-120 minutes, Visit 2 and 3</time_frame>
    <description>Insulin Sensitivity Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting glucose</measure>
    <time_frame>between 0-120 minutes, Visit 2 and 3</time_frame>
    <description>Fasting glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting insulin</measure>
    <time_frame>0-120 minutes, Visit 2 and 3</time_frame>
    <description>Fasting insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Melatonin</measure>
    <time_frame>at baseline and 120 minutes, Visit 2 and 3</time_frame>
    <description>Serum Melatonin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLMO</measure>
    <time_frame>between 0-5 hours, Visit 3</time_frame>
    <description>Dim Light Melatonin Onset</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Temperature record</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Measured using temperature sensor</description>
  </other_outcome>
  <other_outcome>
    <measure>Activity record</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Measured using Acceleration Data Logger</description>
  </other_outcome>
  <other_outcome>
    <measure>Light Exposure</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Measured using a light sensor</description>
  </other_outcome>
  <other_outcome>
    <measure>Sleep Duration</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Sleep duration will be computed from self-reported</description>
  </other_outcome>
  <other_outcome>
    <measure>Total Energy Intake</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Total energy intake in kcal/day will be computed from 7-day 24-hr dietary recalls</description>
  </other_outcome>
  <other_outcome>
    <measure>Dietary Composition</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Macronutrient and micronutrient intake will be computed from 7-days of self-reported 24-hr dietary recalls</description>
  </other_outcome>
  <other_outcome>
    <measure>Dietary Intake Timing</measure>
    <time_frame>total of 1 week between Visit 1 and 2</time_frame>
    <description>Food timing will be self-reported and averaged across 7-days of 24-hr dietary recalls</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical activity</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the International Physical Activity Questionnaire (IPAQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Chronotype</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the Morningness-Eveningness Questionnaire (MEQ).</description>
  </other_outcome>
  <other_outcome>
    <measure>Emotional eating</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the Emotional Eating Questionnaire (EEQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Sleep quality</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the Pittsburgh Sleep Quality Index (PSQI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Insomnia</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the Insomnia Severity Index (ISI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Depression</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessed using the Patient Health Questionnaire (PHQ-9)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Non-Diabetic Disorder of Endocrine Pancreas</condition>
  <arm_group>
    <arm_group_label>MTNR1B CC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Test glucose tolerance in homozygous non-carriers (CC) for MTNR1B rs10830963 in Early OGTT and Late OGTT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MTNR1B GG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Test glucose tolerance in homozygous (GG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MTNR1B CG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Test glucose tolerance in heterozygous (CG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Early OGTT</intervention_name>
    <description>Test glucose tolerance using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)</description>
    <arm_group_label>MTNR1B CC</arm_group_label>
    <arm_group_label>MTNR1B CG</arm_group_label>
    <arm_group_label>MTNR1B GG</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Late OGTT</intervention_name>
    <description>Test glucose tolerance using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)</description>
    <arm_group_label>MTNR1B CC</arm_group_label>
    <arm_group_label>MTNR1B CG</arm_group_label>
    <arm_group_label>MTNR1B GG</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        IInclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index: &gt; 18.5 o &lt; 40 kg/m2&#xD;
&#xD;
          -  Age: between 18 and 65 year of age&#xD;
&#xD;
          -  Caucasian&#xD;
&#xD;
          -  Day workers&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving treatment with thermogenic, lipogenic, or drugs&#xD;
&#xD;
          -  Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis&#xD;
&#xD;
          -  Bulimia diagnosis, prone to binge eating&#xD;
&#xD;
          -  Undergoing treatment with Type 2 diabetes mellitus (high blood sugar) medications such&#xD;
             as Metformin or other non-Metformin oral anti-diabetic drugs such as sulfonylureas,&#xD;
             meglitinides, or glitazones&#xD;
&#xD;
          -  Undergoing treatment with Corticosteroids/steroids, Growth hormone, Anticoagulant&#xD;
             medicines, or blood thinners, Beta blockers for hypertension, Medications for sleep,&#xD;
             Fluvoxamine, Opioids or Amphetamines, Tranquilizers, nonsteroidal anti-inflammatory&#xD;
             drugs.&#xD;
&#xD;
          -  Pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Purificación Gomez Abellan, PHD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidad de Murcia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marta Garaulet, PHD</last_name>
    <phone>678996368</phone>
    <phone_ext>+34</phone_ext>
    <email>garaulet@um.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jesus Lopez-Minguez</last_name>
    <phone>660672851</phone>
    <phone_ext>+34</phone_ext>
    <email>jesus.lopez5@um.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Murcia</name>
      <address>
        <city>Murcia</city>
        <zip>30100</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marta Garaulet, PHD</last_name>
      <phone>678996368</phone>
      <phone_ext>+34</phone_ext>
      <email>garaulet@um.es</email>
    </contact>
    <contact_backup>
      <last_name>Jesus Lopez-Minguez</last_name>
      <phone>660672851</phone>
      <phone_ext>+34</phone_ext>
      <email>jesus.lopez5@um.es</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>February 5, 2020</last_update_submitted>
  <last_update_submitted_qc>February 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad de Murcia</investigator_affiliation>
    <investigator_full_name>PROF. MARTA GARAULET AZA</investigator_full_name>
    <investigator_title>Full Proffesor</investigator_title>
  </responsible_party>
  <keyword>Glucose tolerance test, MTNR1B, nutrigenomics, food timing</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03036592/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03036592/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>December 8, 2020</submitted>
    <returned>January 4, 2021</returned>
    <submitted>May 6, 2021</submitted>
    <returned>June 1, 2021</returned>
    <submitted>June 2, 2022</submitted>
    <returned>March 16, 2023</returned>
  </pending_results>
  <!-- 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/NCT03036592
org study id: 2017ES00001
nct id: NCT03036592
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this investigation is to assess the role of melatonin receptor 1B (MTNR1B)
      single nucleotide polymorphism (SNP)*food timing interaction on glucose control in the
      deleterious effect in a vulnerable population with regular exposure to concurrent high
      melatonin and food intake as late night eaters (those having dinner within 2.5 h before their
      usual bed time). With the results from this study, we expect to advance our understanding of
      the role of endogenous melatonin on glucose metabolism in late night eaters and carriers of
      the MTNR1B risk allele, with potential implications on the guidelines to mitigate risk of
      type 2 diabetes in late night eaters and carriers of the MTNR1B risk allele.
Late-night dinner eating is associated with increased risk for type-2-diabetes. The
      underlying mechanism is unclear. One explanatory hypothesis is that the concurrence of
      elevated circulating melatonin and high glucose concentrations (characterizing late-eating)
      leads to impaired glucose-tolerance. However, to date, no study has tested the influence of
      physiological melatonin concentrations on glucose tolerance. The discovery of melatonin
      receptor MTNR1B as a diabetes risk gene provides evidence for a role of physiological levels
      of melatonin in glucose control.

      The aim of the current study is to test the hypothesis that the concurrence of meal timing
      with elevated endogenous melatonin concentrations results in impaired glucose control and
      that this effect is stronger in homozygous MTNR1B risk carriers than in non-carriers. To do
      so we will test glucose tolerance using identical mixed meals under two glucose oral
      tolerance test (OGTT) conditions: a) delayed OGTT or Late Eating (LE): starting1 hour before
      their usual bed time, b) advanced OGTT or Early Eating (EE): starting 4 hours before habitual
      bed time, in a randomized, cross-over study design.

      These findings could support a clinical application for the screening of this SNP and the
      possibility of implementing tailored and cost-effective behavioral interventions to prevent
      type 2 diabetes in vulnerable populations.

      These goals will be achieved through a specific approach:

      • Interventional (randomized, cross-over controlled trials) (Aim 1): To study the potential
      interaction between meal timing (dinner) and genetic variants MTNR1B for glucose tolerance in
      obese women (n=1000).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Area Under the Curve (AUC) glucose
time frame: between 0-120 minutes, Visit 2 and 3
description: Investigators will measure insulin and glucose levels for 120 minutes at day time and night time visits, and compare them by genotype at selected loci.
measure: Disposition index
time frame: between 0-120 minutes, Visit 2 and 3
description: Disposition index will be determined by frequently sampled oral glucose tolerance test
measure: Corrected Insulin Response
time frame: between 0-120 minutes, Visit 2 and 3
description: Corrected Insulin Response
measure: Insulin Sensitivity Index
time frame: between 0-120 minutes, Visit 2 and 3
description: Insulin Sensitivity Index
measure: Fasting glucose
time frame: between 0-120 minutes, Visit 2 and 3
description: Fasting glucose
measure: Fasting insulin
time frame: 0-120 minutes, Visit 2 and 3
description: Fasting insulin
measure: Serum Melatonin
time frame: at baseline and 120 minutes, Visit 2 and 3
description: Serum Melatonin
measure: DLMO
time frame: between 0-5 hours, Visit 3
description: Dim Light Melatonin Onset
measure: Temperature record
time frame: total of 1 week between Visit 1 and 2
description: Measured using temperature sensor
measure: Activity record
time frame: total of 1 week between Visit 1 and 2
description: Measured using Acceleration Data Logger
measure: Light Exposure
time frame: total of 1 week between Visit 1 and 2
description: Measured using a light sensor
measure: Sleep Duration
time frame: total of 1 week between Visit 1 and 2
description: Sleep duration will be computed from self-reported
measure: Total Energy Intake
time frame: total of 1 week between Visit 1 and 2
description: Total energy intake in kcal/day will be computed from 7-day 24-hr dietary recalls
measure: Dietary Composition
time frame: total of 1 week between Visit 1 and 2
description: Macronutrient and micronutrient intake will be computed from 7-days of self-reported 24-hr dietary recalls
measure: Dietary Intake Timing
time frame: total of 1 week between Visit 1 and 2
description: Food timing will be self-reported and averaged across 7-days of 24-hr dietary recalls
measure: Physical activity
time frame: at baseline
description: Assessed using the International Physical Activity Questionnaire (IPAQ)
measure: Chronotype
time frame: at baseline
description: Assessed using the Morningness-Eveningness Questionnaire (MEQ).
measure: Emotional eating
time frame: at baseline
description: Assessed using the Emotional Eating Questionnaire (EEQ)
measure: Sleep quality
time frame: at baseline
description: Assessed using the Pittsburgh Sleep Quality Index (PSQI)
measure: Insomnia
time frame: at baseline
description: Assessed using the Insomnia Severity Index (ISI)
measure: Depression
time frame: at baseline
description: Assessed using the Patient Health Questionnaire (PHQ-9)
arm group label: MTNR1B CC
arm group type: Experimental
description: Test glucose tolerance in homozygous non-carriers (CC) for MTNR1B rs10830963 in Early OGTT and Late OGTT
arm group label: MTNR1B GG
arm group type: Experimental
description: Test glucose tolerance in homozygous (GG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT
arm group label: MTNR1B CG
arm group type: Experimental
description: Test glucose tolerance in heterozygous (CG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT
intervention type: Behavioral
intervention name: Early OGTT
description: Test glucose tolerance using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)
arm group label: MTNR1B CC
arm group label: MTNR1B CG
arm group label: MTNR1B GG
intervention type: Behavioral
intervention name: Late OGTT
description: Test glucose tolerance using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)
arm group label: MTNR1B CC
arm group label: MTNR1B CG
arm group label: MTNR1B GG
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Purificación Gomez Abellan, PHD
role: Study Chair
affiliation: Universidad de Murcia
last name: Marta Garaulet, PHD
phone: 678996368
phone ext: +34
email: garaulet@um.es
last name: Jesus Lopez-Minguez
phone: 660672851
phone ext: +34
email: jesus.lopez5@um.es
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Universidad de Murcia
investigator full name: PROF. MARTA GARAULET AZA
investigator title: Full Proffesor
sharing ipd: No
provided document: 
provided document: 
submitted: December 8, 2020
returned: January 4, 2021
submitted: May 6, 2021
returned: June 1, 2021
submitted: June 2, 2022
returned: March 16, 2023