<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/NCT03025347</url>
  </required_header>
  <id_info>
    <org_study_id>R14-P143</org_study_id>
    <nct_id>NCT03025347</nct_id>
  </id_info>
  <brief_title>Effect of Exercise on Appetite, Gut Peptides and Butyrylcholinesterase Activity in Variants of the FTO Gene</brief_title>
  <official_title>Effect of Exercise on Appetite, Energy Intake, Butyrylcholinesterase Activity and Gut Peptides in Men With Variants of the Obesity-linked FTO rs9939609 Polymorphism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loughborough University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rosetrees Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Loughborough University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Using a database of individuals with FTO genetic data, the study aims to assess the appetite,&#xD;
      energy intake, butyrylcholinesterase, gut hormone responses to a bout of moderate- to high&#xD;
      intensity exercise in individuals with genetic variations in the FTO gene.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The fat mass and obesity-associated gene (FTO) rs9939609 A allele is related to obesity,&#xD;
      greater food intake and impaired postprandial reduction of ghrelin. Exercise acutely&#xD;
      suppresses levels of ghrelin and appetite, yet whether the response differs in people with or&#xD;
      without the rs9939609 A allele is unknown. This study assessed the effect of exercise on&#xD;
      appetite, appetite-regulatory hormones and energy intake in variants of the FTO rs9939609&#xD;
      polymorphism.&#xD;
&#xD;
      Cohort&#xD;
&#xD;
      The investigators initially recruited 202 subjects to a database and measured FTO rs9939609&#xD;
      genotype. From these subjects, 12 individuals homozygous for the 'obesity-risk' rs9939609 A&#xD;
      allele and 12 homozygous for the T allele were recruited.&#xD;
&#xD;
      A sample size of 24 was chosen based on previous data which suggested that a 34 pg/ml&#xD;
      reduction in circulating acylated ghrelin during exercise could be detected with &gt; 80% power&#xD;
      with a two-tailed t-test whilst assuming a standard deviation of differences of 54 pg/ml.&#xD;
&#xD;
      Familiarisation trial&#xD;
&#xD;
      First, participants will arrive for a familiarisation trial. Participants will have been&#xD;
      fasted for ~2-3 hours beforehand. Participant's height, weight and skinfold measures will be&#xD;
      taken. Furthermore, a food preferences questionnaire will be completed to ensure the&#xD;
      acceptability of food items provided during the study.&#xD;
&#xD;
      Participants will complete a sub-maximal fitness test, which will last for 16 minutes, and&#xD;
      will comprise of four, four minute stages. Initial treadmill speed will be set according to&#xD;
      fitness and will be increased every four minutes by 0.5-1.5 km/h. Prior to this test,&#xD;
      participants will be fitted with a cannula into an antecubital vein and a blood sample will&#xD;
      be withdrawn after the test. This will familiarise participants with the procedure and reduce&#xD;
      any stress related to the novelty of the first visit.&#xD;
&#xD;
      Next, a maximal fitness test will be conducted to measure maximal oxygen uptake. This will&#xD;
      consist of an incremental protocol where the treadmill gradient will begin at 3.5% and will&#xD;
      be increased by 2.5% every 3 minutes. The speed of treadmill will remain constant, and will&#xD;
      be determined based on fitness levels. Though the duration of the test is typically 9-15&#xD;
      minutes, it will last until the participant reaches volitional exhaustion.&#xD;
&#xD;
      After the fitness test and adequate recovery time, participants will be presented with a&#xD;
      buffet-style meal and instructed to eat until comfortably full and satisfied. To finish,&#xD;
      participants will be given a calibrated set of weighing scales and instructions to&#xD;
      standardize their food intake before each main trial.&#xD;
&#xD;
      Main trials&#xD;
&#xD;
      Each participant will complete two main trials separated by 7 days: an exercise trial and&#xD;
      control trial. In the 24 hours before a main trial, participants will follow a set of&#xD;
      standardization procedures. Participants will record all foods consumed and the timings of&#xD;
      meals before the first trial. This will be subsequently replicated in the 24 hours prior to&#xD;
      the second main trial. Moreover, participants will visit the lab to be provided with a meal&#xD;
      and will be instructed to prepare and consume between 19:00-20:00 the night before each main&#xD;
      trial. Participants will also be instructed to refrain from strenuous physical activity and&#xD;
      alcohol consumption during this period.&#xD;
&#xD;
      Participants will report to the lab on the morning of each trial at 08:00 following an&#xD;
      overnight fast. Participants will be instructed to walk slowly to the lab in the morning of&#xD;
      each trial.&#xD;
&#xD;
      At 08:30, a cannula will be inserted into an antecubital vein followed by 60 minutes of rest.&#xD;
      On the exercise trial, from 09:30 to 10:30, participants will run at a continuous pace that&#xD;
      corresponds to 70% of the participant's maximal oxygen uptake. Participants will rest on the&#xD;
      bed during this same period of the control trial. Participants will rest and will be provided&#xD;
      with a selection of movies to watch for the rest of the trial.&#xD;
&#xD;
      There will be two meals provided to the participants: a standardised meal and an ad libitum&#xD;
      buffet style meal. The standardised meal will be a fixed breakfast meal that participants&#xD;
      will be provided at 10:50, and will be instructed to consume within 20 minutes. The ad&#xD;
      libitum buffet style meal will be given at 15:50 and will consist of an array of foods with&#xD;
      differing energy and macronutrient compositions. Participants will be presented with the&#xD;
      buffet foods for 30 minutes and will be instructed to eat until comfortably full and&#xD;
      satisfied.&#xD;
&#xD;
      Statistical procedures&#xD;
&#xD;
      Linear mixed model, with factors being trial (exercise or control), genotype (AA or TT) and&#xD;
      time will be performed on all time-course measures. Area under the curve will be calculated&#xD;
      using the trapezoidal rule for outcome measures taken periodically throughout the day. Linear&#xD;
      mixed models will also be used for trial and genotype comparisons of area under the curve&#xD;
      values and measures not taken throughout the day. At points of interest, where significant&#xD;
      main and interaction effects occur, post-hoc analysis was conducted using Holm-Bonferroni&#xD;
      adjusted t-tests. Statistical significance was accepted as P &lt; 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Plasma acylated ghrelin concentrations (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured using ELISA from venous blood samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma desacyl ghrelin concentrations (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured using ELISA from venous blood samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective appetite (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured using visual analogue scales</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ad-libitum energy intake (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured at laboratory-based meals</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma butyrylcholinesterase activity (N=24)</measure>
    <time_frame>First hour of main trial (three samples).</time_frame>
    <description>Measured using Ellman's reagent protocol</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma total glucagon-like peptide 1 concentrations (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured using ELISA from venous blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma total peptide yy concentrations (N=24)</measure>
    <time_frame>24 hours</time_frame>
    <description>Measured using ELISA from venous blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma leptin concentrations (N=24)</measure>
    <time_frame>Baseline (fasting) sample</time_frame>
    <description>Measured using ELISA from venous blood samples</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Appetitive Behavior</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental day where participants rest.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental day where participants complete a run.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>Participants complete a resting control condition instead of a run.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Participants complete a 60 minute run at 70% of their maximal oxygen uptake</description>
    <arm_group_label>Exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  non-smoker, not currently dieting, weight stable for &gt;3 months (self-reported), no&#xD;
             personal history of cardiovascular disease, metabolic disease or dyslipidaemia,&#xD;
             European ancestry, no psychiatric or medical condition&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  food allergies, dislike or intolerance of study foods and drinks, irregular eating&#xD;
             patterns, use of medication that could influence hormone concentrations&#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>David J Stensel, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loughborough University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loughborough University</name>
      <address>
        <city>Loughborough</city>
        <zip>LE11 3TU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. doi: 10.1126/science.1141634. Epub 2007 Apr 12.</citation>
    <PMID>17434869</PMID>
  </reference>
  <reference>
    <citation>Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring). 2008 Aug;16(8):1961-5. doi: 10.1038/oby.2008.318. Epub 2008 Jun 12.</citation>
    <PMID>18551109</PMID>
  </reference>
  <reference>
    <citation>Karra E, O'Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Ruther UU, Bruning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug;123(8):3539-51. doi: 10.1172/JCI44403. Epub 2013 Jul 15.</citation>
    <PMID>23867619</PMID>
  </reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>February 5, 2019</last_update_submitted>
  <last_update_submitted_qc>February 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loughborough University</investigator_affiliation>
    <investigator_full_name>Professor David Stensel</investigator_full_name>
    <investigator_title>Professor of Exercise Metabolism</investigator_title>
  </responsible_party>
  <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/NCT03025347
org study id: R14-P143
nct id: NCT03025347
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Using a database of individuals with FTO genetic data, the study aims to assess the appetite,
      energy intake, butyrylcholinesterase, gut hormone responses to a bout of moderate- to high
      intensity exercise in individuals with genetic variations in the FTO gene.
The fat mass and obesity-associated gene (FTO) rs9939609 A allele is related to obesity,
      greater food intake and impaired postprandial reduction of ghrelin. Exercise acutely
      suppresses levels of ghrelin and appetite, yet whether the response differs in people with or
      without the rs9939609 A allele is unknown. This study assessed the effect of exercise on
      appetite, appetite-regulatory hormones and energy intake in variants of the FTO rs9939609
      polymorphism.

      Cohort

      The investigators initially recruited 202 subjects to a database and measured FTO rs9939609
      genotype. From these subjects, 12 individuals homozygous for the 'obesity-risk' rs9939609 A
      allele and 12 homozygous for the T allele were recruited.

      A sample size of 24 was chosen based on previous data which suggested that a 34 pg/ml
      reduction in circulating acylated ghrelin during exercise could be detected with > 80% power
      with a two-tailed t-test whilst assuming a standard deviation of differences of 54 pg/ml.

      Familiarisation trial

      First, participants will arrive for a familiarisation trial. Participants will have been
      fasted for ~2-3 hours beforehand. Participant's height, weight and skinfold measures will be
      taken. Furthermore, a food preferences questionnaire will be completed to ensure the
      acceptability of food items provided during the study.

      Participants will complete a sub-maximal fitness test, which will last for 16 minutes, and
      will comprise of four, four minute stages. Initial treadmill speed will be set according to
      fitness and will be increased every four minutes by 0.5-1.5 km/h. Prior to this test,
      participants will be fitted with a cannula into an antecubital vein and a blood sample will
      be withdrawn after the test. This will familiarise participants with the procedure and reduce
      any stress related to the novelty of the first visit.

      Next, a maximal fitness test will be conducted to measure maximal oxygen uptake. This will
      consist of an incremental protocol where the treadmill gradient will begin at 3.5% and will
      be increased by 2.5% every 3 minutes. The speed of treadmill will remain constant, and will
      be determined based on fitness levels. Though the duration of the test is typically 9-15
      minutes, it will last until the participant reaches volitional exhaustion.

      After the fitness test and adequate recovery time, participants will be presented with a
      buffet-style meal and instructed to eat until comfortably full and satisfied. To finish,
      participants will be given a calibrated set of weighing scales and instructions to
      standardize their food intake before each main trial.

      Main trials

      Each participant will complete two main trials separated by 7 days: an exercise trial and
      control trial. In the 24 hours before a main trial, participants will follow a set of
      standardization procedures. Participants will record all foods consumed and the timings of
      meals before the first trial. This will be subsequently replicated in the 24 hours prior to
      the second main trial. Moreover, participants will visit the lab to be provided with a meal
      and will be instructed to prepare and consume between 19:00-20:00 the night before each main
      trial. Participants will also be instructed to refrain from strenuous physical activity and
      alcohol consumption during this period.

      Participants will report to the lab on the morning of each trial at 08:00 following an
      overnight fast. Participants will be instructed to walk slowly to the lab in the morning of
      each trial.

      At 08:30, a cannula will be inserted into an antecubital vein followed by 60 minutes of rest.
      On the exercise trial, from 09:30 to 10:30, participants will run at a continuous pace that
      corresponds to 70% of the participant's maximal oxygen uptake. Participants will rest on the
      bed during this same period of the control trial. Participants will rest and will be provided
      with a selection of movies to watch for the rest of the trial.

      There will be two meals provided to the participants: a standardised meal and an ad libitum
      buffet style meal. The standardised meal will be a fixed breakfast meal that participants
      will be provided at 10:50, and will be instructed to consume within 20 minutes. The ad
      libitum buffet style meal will be given at 15:50 and will consist of an array of foods with
      differing energy and macronutrient compositions. Participants will be presented with the
      buffet foods for 30 minutes and will be instructed to eat until comfortably full and
      satisfied.

      Statistical procedures

      Linear mixed model, with factors being trial (exercise or control), genotype (AA or TT) and
      time will be performed on all time-course measures. Area under the curve will be calculated
      using the trapezoidal rule for outcome measures taken periodically throughout the day. Linear
      mixed models will also be used for trial and genotype comparisons of area under the curve
      values and measures not taken throughout the day. At points of interest, where significant
      main and interaction effects occur, post-hoc analysis was conducted using Holm-Bonferroni
      adjusted t-tests. Statistical significance was accepted as P < 0.05.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Plasma acylated ghrelin concentrations (N=24)
time frame: 24 hours
description: Measured using ELISA from venous blood samples
measure: Plasma desacyl ghrelin concentrations (N=24)
time frame: 24 hours
description: Measured using ELISA from venous blood samples
measure: Subjective appetite (N=24)
time frame: 24 hours
description: Measured using visual analogue scales
measure: Ad-libitum energy intake (N=24)
time frame: 24 hours
description: Measured at laboratory-based meals
measure: Plasma butyrylcholinesterase activity (N=24)
time frame: First hour of main trial (three samples).
description: Measured using Ellman's reagent protocol
measure: Plasma total glucagon-like peptide 1 concentrations (N=24)
time frame: 24 hours
description: Measured using ELISA from venous blood samples
measure: Plasma total peptide yy concentrations (N=24)
time frame: 24 hours
description: Measured using ELISA from venous blood samples
measure: Plasma leptin concentrations (N=24)
time frame: Baseline (fasting) sample
description: Measured using ELISA from venous blood samples
arm group label: Control
arm group type: Experimental
description: Experimental day where participants rest.
arm group label: Exercise
arm group type: Experimental
description: Experimental day where participants complete a run.
intervention type: Other
intervention name: Control
description: Participants complete a resting control condition instead of a run.
arm group label: Control
intervention type: Other
intervention name: Exercise
description: Participants complete a 60 minute run at 70% of their maximal oxygen uptake
arm group label: Exercise
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David J Stensel, PhD
role: Principal Investigator
affiliation: Loughborough University
facility: 
country: United Kingdom
citation: Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. doi: 10.1126/science.1141634. Epub 2007 Apr 12.
PMID: 17434869
citation: Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring). 2008 Aug;16(8):1961-5. doi: 10.1038/oby.2008.318. Epub 2008 Jun 12.
PMID: 18551109
citation: Karra E, O'Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Ruther UU, Bruning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug;123(8):3539-51. doi: 10.1172/JCI44403. Epub 2013 Jul 15.
PMID: 23867619
responsible party type: Principal Investigator
investigator affiliation: Loughborough University
investigator full name: Professor David Stensel
investigator title: Professor of Exercise Metabolism
sharing ipd: No