<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/NCT03771690</url>
  </required_header>
  <id_info>
    <org_study_id>R17-P178</org_study_id>
    <nct_id>NCT03771690</nct_id>
  </id_info>
  <brief_title>Individual Variability of Appetite Responses to a Standardised Meal</brief_title>
  <official_title>A Replicated Crossover Study to Explore Individual Variability of Appetite Responses to a Standardised Meal and Any Moderating Influence of the FTO Gene</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loughborough University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Teesside University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Loughborough 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>
      The aim of this study is to examine the interindividual variability of subjective and&#xD;
      hormonal appetite responses to a standardised meal in healthy men and explore any moderating&#xD;
      influence of the fat mass and obesity associated gene (FTO).&#xD;
&#xD;
      Participants homozygous for the obesity risk A allele (AA) or low risk T allele (TT) of FTO&#xD;
      rs9939609 will complete two fasted control and two standardised meal (5025 kJ energy, 47%&#xD;
      carbohydrate, 9% protein, 44% fat) conditions in randomised sequences. Ratings of perceived&#xD;
      appetite and venous blood samples will be taken before and after the interventions.&#xD;
      Interindividual differences in appetite responses and the potential moderating influence of&#xD;
      the FTO gene will be examined using bivariate correlations and linear mixed modelling.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Meal ingestion initiates a series of co-ordinated subjective and hormonal appetite responses.&#xD;
      However, it is not known whether interindividual variability in appetite exists in response&#xD;
      to a standardised meal. A recent approach proposed to quantify individual differences in the&#xD;
      intervention response involves quantifying the participant-by-response interaction from&#xD;
      replicated intervention and comparator arms. Using this approach (a replicated crossover&#xD;
      study), the current study will (1) investigate whether the perceived appetite and&#xD;
      appetite-related hormone responses to a standardised meal are reproducible on repeated&#xD;
      occasions; (2) examine whether there is true individual variability in appetite responses to&#xD;
      a standardised meal; and (3) determine whether the fat mass and obesity associated gene (FTO)&#xD;
      moderates the magnitude of appetite responses to a standardised meal.&#xD;
&#xD;
      A total of 18 healthy men will be recruited according to their FTO rs9939609 genotype: 9&#xD;
      homozygous minor allele (AA) and 9 homozygous major allele (TT). Participants will complete&#xD;
      four main experimental conditions each separated by an interval of at least three days: two&#xD;
      fasted control and two standardised meal conditions. Participants will arrive at the&#xD;
      laboratory at 09:00 after a 13 h overnight fast and a cannula will be inserted into an&#xD;
      antecubital vein for blood sampling. After 60 min rest, a fasting venous blood sample and&#xD;
      rating of perceived appetite will be taken (0 h; 10:00). Participants will rest throughout&#xD;
      all four conditions but will be provided with a standardised breakfast meal after the fasting&#xD;
      measurements during the two meal conditions. Breakfast will be consumed within 15 min and&#xD;
      consist of croissants, butter, chocolate spread, cereal biscuits and milkshake which will&#xD;
      provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat). Subsequent venous blood&#xD;
      samples will be taken at 0.5 h (10:30) and 1 h (11:00), and appetite perceptions will be&#xD;
      assessed at 1 h (11:00).&#xD;
&#xD;
      Interindividual differences will be explored by correlating the two sets of response&#xD;
      differences between meal and control conditions. Within-participant covariate-adjusted linear&#xD;
      mixed models will be used to quantify participant-by-condition and FTO genotype-by-condition&#xD;
      interactions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2018</start_date>
  <completion_date type="Actual">May 1, 2018</completion_date>
  <primary_completion_date type="Actual">May 1, 2018</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acylated ghrelin concentration</measure>
    <time_frame>1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in plasma acylated ghrelin concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total peptide YY concentration</measure>
    <time_frame>1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in plasma total peptide YY concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin concentration</measure>
    <time_frame>0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in plasma insulin concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose concentration</measure>
    <time_frame>0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in plasma glucose concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rating of perceived hunger</measure>
    <time_frame>1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in rating of perceived hunger. Perceived hunger will be measured using a 100 mm visual analogue scale anchored at 0, 'I am not hungry at all', and 100, 'I have never been more hungry'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rating of perceived satisfaction</measure>
    <time_frame>1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in rating of perceived satisfaction. Perceived satisfaction will be measured using a 100 mm visual analogue scale anchored at 0, 'I am completely empty', and 100, 'I cannot eat another bite'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rating of perceived fullness</measure>
    <time_frame>1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in rating of perceived fullness. Perceived fullness will be measured using a 100 mm visual analogue scale anchored at 0, 'Not full at all', and 100, 'Totally full'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rating of perceived prospective food consumption</measure>
    <time_frame>1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))</time_frame>
    <description>Control adjusted pre-to-post change in rating of perceived prospective food consumption. Perceived prospective food consumption will be measured using a 100 mm visual analogue scale anchored at 0, 'Nothing at all', and 100, 'A lot'.&#xD;
consumption</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Appetitive Behavior</condition>
  <condition>Obesity</condition>
  <condition>Genetic Predisposition to Disease</condition>
  <arm_group>
    <arm_group_label>Control 1</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control 2</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standardised meal 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00). A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standardised meal 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00). A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Standardised meal</intervention_name>
    <description>A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).</description>
    <arm_group_label>Standardised meal 1</arm_group_label>
    <arm_group_label>Standardised meal 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Homozygous minor allele (AA) or major allele (TT) FTO rs9939609 genotype;&#xD;
&#xD;
          -  Non-smoker;&#xD;
&#xD;
          -  Weight stable for the previous 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Heterozygous FTO rs9939609 genotype (i.e., AT);&#xD;
&#xD;
          -  Any medical conditions (e.g., diabetes, coagulation or bleeding disorders);&#xD;
&#xD;
          -  Taking any medication that might influence appetite, fat metabolism or blood glucose;&#xD;
&#xD;
          -  Dieting or restrained eating behaviours;&#xD;
&#xD;
          -  Any food allergies.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Stensel</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loughborough University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fernanda Reistenbach Goltz</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loughborough University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Greg Atkinson</last_name>
    <role>Principal Investigator</role>
    <affiliation>Teesside University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loughborough University</name>
      <address>
        <city>Loughborough</city>
        <state>Leicestershire</state>
        <zip>LE11 3TU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Goltz FR, Thackray AE, King JA, Dorling JL, Atkinson G, Stensel DJ. Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study. Med Sci Sports Exerc. 2018 Apr;50(4):758-768. doi: 10.1249/MSS.0000000000001504.</citation>
    <PMID>29240652</PMID>
  </reference>
  <reference>
    <citation>Atkinson G, Batterham AM. True and false interindividual differences in the physiological response to an intervention. Exp Physiol. 2015 Jun;100(6):577-88. doi: 10.1113/EP085070. Epub 2015 May 13.</citation>
    <PMID>25823596</PMID>
  </reference>
  <reference>
    <citation>Senn S, Rolfe K, Julious SA. Investigating variability in patient response to treatment--a case study from a replicate cross-over study. Stat Methods Med Res. 2011 Dec;20(6):657-66. doi: 10.1177/0962280210379174. Epub 2010 Aug 25.</citation>
    <PMID>20739334</PMID>
  </reference>
  <reference>
    <citation>Senn S. Mastering variation: variance components and personalised medicine. Stat Med. 2016 Mar 30;35(7):966-77. doi: 10.1002/sim.6739. Epub 2015 Sep 28.</citation>
    <PMID>26415869</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 8, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>December 8, 2018</last_update_submitted>
  <last_update_submitted_qc>December 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loughborough University</investigator_affiliation>
    <investigator_full_name>Fernanda Reistenbach Goltz</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Appetite</keyword>
  <keyword>FTO</keyword>
  <keyword>Ghrelin</keyword>
  <keyword>Individual variability</keyword>
  <keyword>Meal intake</keyword>
  <keyword>Peptide YY</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genetic Predisposition to Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 3, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03771690/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03771690
org study id: R17-P178
nct id: NCT03771690
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to examine the interindividual variability of subjective and
      hormonal appetite responses to a standardised meal in healthy men and explore any moderating
      influence of the fat mass and obesity associated gene (FTO).

      Participants homozygous for the obesity risk A allele (AA) or low risk T allele (TT) of FTO
      rs9939609 will complete two fasted control and two standardised meal (5025 kJ energy, 47%
      carbohydrate, 9% protein, 44% fat) conditions in randomised sequences. Ratings of perceived
      appetite and venous blood samples will be taken before and after the interventions.
      Interindividual differences in appetite responses and the potential moderating influence of
      the FTO gene will be examined using bivariate correlations and linear mixed modelling.
Meal ingestion initiates a series of co-ordinated subjective and hormonal appetite responses.
      However, it is not known whether interindividual variability in appetite exists in response
      to a standardised meal. A recent approach proposed to quantify individual differences in the
      intervention response involves quantifying the participant-by-response interaction from
      replicated intervention and comparator arms. Using this approach (a replicated crossover
      study), the current study will (1) investigate whether the perceived appetite and
      appetite-related hormone responses to a standardised meal are reproducible on repeated
      occasions; (2) examine whether there is true individual variability in appetite responses to
      a standardised meal; and (3) determine whether the fat mass and obesity associated gene (FTO)
      moderates the magnitude of appetite responses to a standardised meal.

      A total of 18 healthy men will be recruited according to their FTO rs9939609 genotype: 9
      homozygous minor allele (AA) and 9 homozygous major allele (TT). Participants will complete
      four main experimental conditions each separated by an interval of at least three days: two
      fasted control and two standardised meal conditions. Participants will arrive at the
      laboratory at 09:00 after a 13 h overnight fast and a cannula will be inserted into an
      antecubital vein for blood sampling. After 60 min rest, a fasting venous blood sample and
      rating of perceived appetite will be taken (0 h; 10:00). Participants will rest throughout
      all four conditions but will be provided with a standardised breakfast meal after the fasting
      measurements during the two meal conditions. Breakfast will be consumed within 15 min and
      consist of croissants, butter, chocolate spread, cereal biscuits and milkshake which will
      provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat). Subsequent venous blood
      samples will be taken at 0.5 h (10:30) and 1 h (11:00), and appetite perceptions will be
      assessed at 1 h (11:00).

      Interindividual differences will be explored by correlating the two sets of response
      differences between meal and control conditions. Within-participant covariate-adjusted linear
      mixed models will be used to quantify participant-by-condition and FTO genotype-by-condition
      interactions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Acylated ghrelin concentration
time frame: 1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in plasma acylated ghrelin concentration
measure: Total peptide YY concentration
time frame: 1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in plasma total peptide YY concentration
measure: Insulin concentration
time frame: 0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))
description: Control adjusted pre-to-post change in plasma insulin concentration
measure: Glucose concentration
time frame: 0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))
description: Control adjusted pre-to-post change in plasma glucose concentration
measure: Rating of perceived hunger
time frame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in rating of perceived hunger. Perceived hunger will be measured using a 100 mm visual analogue scale anchored at 0, 'I am not hungry at all', and 100, 'I have never been more hungry'.
measure: Rating of perceived satisfaction
time frame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in rating of perceived satisfaction. Perceived satisfaction will be measured using a 100 mm visual analogue scale anchored at 0, 'I am completely empty', and 100, 'I cannot eat another bite'.
measure: Rating of perceived fullness
time frame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in rating of perceived fullness. Perceived fullness will be measured using a 100 mm visual analogue scale anchored at 0, 'Not full at all', and 100, 'Totally full'.
measure: Rating of perceived prospective food consumption
time frame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
description: Control adjusted pre-to-post change in rating of perceived prospective food consumption. Perceived prospective food consumption will be measured using a 100 mm visual analogue scale anchored at 0, 'Nothing at all', and 100, 'A lot'.
consumption
arm group label: Control 1
arm group type: No Intervention
description: After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00).
arm group label: Control 2
arm group type: No Intervention
description: After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00).
arm group label: Standardised meal 1
arm group type: Experimental
description: After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00). A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).
arm group label: Standardised meal 2
arm group type: Experimental
description: After a 13 h overnight fast, participants will rest in the laboratory for the duration of the trial (09:00-11:00). A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).
intervention type: Behavioral
intervention name: Standardised meal
description: A standardised meal will be consumed at 10:00 which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat).
arm group label: Standardised meal 1
arm group label: Standardised meal 2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Stensel
role: Principal Investigator
affiliation: Loughborough University
last name: Fernanda Reistenbach Goltz
role: Principal Investigator
affiliation: Loughborough University
last name: Greg Atkinson
role: Principal Investigator
affiliation: Teesside University
facility: 
country: United Kingdom
citation: Goltz FR, Thackray AE, King JA, Dorling JL, Atkinson G, Stensel DJ. Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study. Med Sci Sports Exerc. 2018 Apr;50(4):758-768. doi: 10.1249/MSS.0000000000001504.
PMID: 29240652
citation: Atkinson G, Batterham AM. True and false interindividual differences in the physiological response to an intervention. Exp Physiol. 2015 Jun;100(6):577-88. doi: 10.1113/EP085070. Epub 2015 May 13.
PMID: 25823596
citation: Senn S, Rolfe K, Julious SA. Investigating variability in patient response to treatment--a case study from a replicate cross-over study. Stat Methods Med Res. 2011 Dec;20(6):657-66. doi: 10.1177/0962280210379174. Epub 2010 Aug 25.
PMID: 20739334
citation: Senn S. Mastering variation: variance components and personalised medicine. Stat Med. 2016 Mar 30;35(7):966-77. doi: 10.1002/sim.6739. Epub 2015 Sep 28.
PMID: 26415869
responsible party type: Principal Investigator
investigator affiliation: Loughborough University
investigator full name: Fernanda Reistenbach Goltz
investigator title: Principal Investigator
mesh term: Genetic Predisposition to Disease
sharing ipd: No
provided document: 