<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/NCT04417205</url>
  </required_header>
  <id_info>
    <org_study_id>DC-I</org_study_id>
    <nct_id>NCT04417205</nct_id>
  </id_info>
  <brief_title>Isolating and Exploiting the Mechanisms That Link Breakfast and Human Health - Intervention</brief_title>
  <official_title>Isolating and Exploiting the Mechanisms That Link Breakfast and Human Health - Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bath</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bath</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>
      Following the establishment of causal links between breakfast consumption, the individual&#xD;
      components of energy balance, and health it is now important to examine and target the&#xD;
      underlying biological mechanisms involved to maximise potential health benefits.&#xD;
&#xD;
      To begin investigating the outlined mechanisms healthy, non-obese participants will be&#xD;
      recruited to take part in phase I (acute design) of a wider project.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Causal links between breakfast consumption, the individual components of energy balance, and&#xD;
      health have recently been established and it is now important to examine and target the&#xD;
      underlying biological mechanisms over a longer period of time to maximise potential health&#xD;
      benefits.&#xD;
&#xD;
      Specifically, the substitution of a portion of carbohydrate for protein at breakfast may&#xD;
      enhance the potential health benefits of breakfast through targeting distinct mechanistic&#xD;
      pathways. Broadly, introducing a greater protein load at breakfast increases insulin&#xD;
      secretion and delays gastric emptying, thereby eliciting a potentiated insulin response. In&#xD;
      turn this may therefore improve glucose tolerance during a subsequent meal. Additionally,&#xD;
      maintenance of euglycaemia following breakfast consumption, coupled with the thermic effect&#xD;
      of feeding protein may accentuate the elevated energy expenditure following breakfast&#xD;
      observed in previous studies. Finally, both the physical and chemical properties of protein&#xD;
      exert a marked satiating effect. Collectively, these mechanisms could interact to maximise&#xD;
      the net impact of breakfast on energy balance and associated health outcomes. However, whilst&#xD;
      the evidence indicates obvious benefits of feeding a higher protein dose at breakfast,&#xD;
      relatively little research has focused on the response to protein over multiple meals/days.&#xD;
      Furthermore, and importantly, the mechanisms involved in the second-meal phenomenon and the&#xD;
      potential for initial meals of varied composition to target these mechanisms have never been&#xD;
      systematically investigated.&#xD;
&#xD;
      To begin investigating the outlined mechanisms healthy, non-obese participants will be&#xD;
      recruited to undergo a 4 week intervention study in which they will consume one of three&#xD;
      breakfasts for 28-days. The breakfast interventions provide will be:&#xD;
&#xD;
      Carbohydrate rich breakfast&#xD;
&#xD;
      Whey protein enriched breakfast&#xD;
&#xD;
      Extended morning fast&#xD;
&#xD;
      Participants will undergo 7 days of habitual physical activity and diet monitoring prior to&#xD;
      visiting the laboratory for their preliminary metabolic assessment in which they will consume&#xD;
      the carbohydrate rich breakfast followed by an ad libitum meal for lunch. They will then be&#xD;
      randomised to one of the 3 breakfast interventions for 28-days. During the 28-days weekly&#xD;
      monitoring of physical activity and energy intake will take place in order to assess energy&#xD;
      balance.&#xD;
&#xD;
      Upon completion of the intervention phase participants will revisit the laboratory to&#xD;
      replicate the initial visit in which postprandial metabolism was assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 26, 2019</start_date>
  <completion_date type="Actual">August 1, 2022</completion_date>
  <primary_completion_date type="Actual">August 1, 2022</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be randomised to one of 3 intervention arms.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Where applicable (i.e. the two breakfast feeding interventions) participants will be blinded to the breakfast that they receive for 28-days.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in physical activity thermogenesis</measure>
    <time_frame>Assessed for 1 week at baseline, 3 days a week during weeks 1-3 of the intervention and again for 1 week in the 4th week of the intervention.</time_frame>
    <description>Energy expenditure measured using physical activity monitor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in expression of circadian clock genes measured in whole blood</measure>
    <time_frame>Baseline and 4-weeks</time_frame>
    <description>Pre and post intervention change clock gene expression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in postprandial glycaemia following carbohydrate rich test breakfast and lunch over 4 weeks</measure>
    <time_frame>Baseline and 4-weeks</time_frame>
    <description>The postprandial time course response of plasma glucose to the test breakfast and lunch meals</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in postprandial insulinaemia following carbohydrate rich test breakfast and lunch over 4 weeks</measure>
    <time_frame>Assessed at baseline and after 4 weeks of the intervention</time_frame>
    <description>The postprandial time course response of plasma insulin to the test breakfast and lunch meals</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in body mass</measure>
    <time_frame>4 weeks</time_frame>
    <description>Participants will be weighed prior to the intervention and again upon completion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in postprandial incretin hormone response following breakfast and lunch</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>The postprandial time course response of plasma incretin hormones (e.g. GLP-1 &amp; GIP) to the the test breakfast.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in subjective appetite ratings following breakfast and lunch</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Ratings of appetite provided on subjective appetite scales (on a scale of 0-100 mm where 0 is associated with lower ratings and 100 with higher ratings) following the test breakfast and lunch</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fuel oxidation during the test breakfast</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Fat and carbohydrate oxidation following breakfast</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Physical Activity</condition>
  <condition>Postprandial Metabolism</condition>
  <condition>Weight Loss</condition>
  <arm_group>
    <arm_group_label>Carbohydrate rich breakfast</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be provided with 28-days worth of pre-weighed carbohydrate rich breakfast materials to consume before 1000h daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whey protein enriched breakfast</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be provided with 28-days worth of pre-weighed whey protein enriched rich breakfast materials to consume before 1000h daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Extended morning fast</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will be asked to remain fasted (i.e. to not consume breakfast) until 1200h daily for 28-days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Carbohydrate Rich Breakfast</intervention_name>
    <description>Participants will be asked to consume the provided carbohydrate rich breakfast before 1000h daily for 28 days.</description>
    <arm_group_label>Carbohydrate rich breakfast</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Whey protein enriched breakfast</intervention_name>
    <description>Participants will be asked to consume the provided whey protein enriched breakfast before 1000h daily for 28 days.</description>
    <arm_group_label>Whey protein enriched breakfast</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index 18.5-29.9 kg∙m-2&#xD;
&#xD;
          -  Age 18-65 years&#xD;
&#xD;
          -  Able and willing to provide informed consent and safely comply with study procedures&#xD;
&#xD;
          -  Females to maintain record of regular menstrual cycle phase or contraceptive use&#xD;
&#xD;
          -  No anticipated changes in diet/physical activity during the study (e.g. holidays or&#xD;
             diet plans)&#xD;
&#xD;
          -  Inclusive to all breakfast habits (e.g. regular skipper / consumer)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any reported condition or behaviour deemed either to pose undue personal risk to the&#xD;
             participant or introduce bias&#xD;
&#xD;
          -  Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)&#xD;
&#xD;
          -  Any reported use of substances which may pose undue personal risk to the participants&#xD;
             or introduce bias into the experiment (e.g. smoking/substance abuse)&#xD;
&#xD;
          -  Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)&#xD;
&#xD;
          -  Any reported recent (&lt;6 months) change in body mass (± 3%)&#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>Harry A Smith, MSci</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Bath</affiliation>
  </overall_official>
  <overall_official>
    <last_name>James A Betts, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Bath</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Bath</name>
      <address>
        <city>Bath</city>
        <state>Somerset</state>
        <zip>BA2 7AY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Leidy HJ, Ortinau LC, Douglas SM, Hoertel HA. Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, &quot;breakfast-skipping,&quot; late-adolescent girls. Am J Clin Nutr. 2013 Apr;97(4):677-88. doi: 10.3945/ajcn.112.053116. Epub 2013 Feb 27.</citation>
    <PMID>23446906</PMID>
  </reference>
  <reference>
    <citation>Bray GA, Redman LM, de Jonge L, Covington J, Rood J, Brock C, Mancuso S, Martin CK, Smith SR. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber. Am J Clin Nutr. 2015 Mar;101(3):496-505. doi: 10.3945/ajcn.114.091769. Epub 2015 Jan 14.</citation>
    <PMID>25733634</PMID>
  </reference>
  <reference>
    <citation>Park YM, Heden TD, Liu Y, Nyhoff LM, Thyfault JP, Leidy HJ, Kanaley JA. A high-protein breakfast induces greater insulin and glucose-dependent insulinotropic peptide responses to a subsequent lunch meal in individuals with type 2 diabetes. J Nutr. 2015 Mar;145(3):452-8. doi: 10.3945/jn.114.202549. Epub 2014 Dec 24.</citation>
    <PMID>25733459</PMID>
  </reference>
  <reference>
    <citation>Chowdhury EA, Richardson JD, Holman GD, Tsintzas K, Thompson D, Betts JA. The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults. Am J Clin Nutr. 2016 Mar;103(3):747-56. doi: 10.3945/ajcn.115.122044. Epub 2016 Feb 10.</citation>
    <PMID>26864365</PMID>
  </reference>
  <reference>
    <citation>Betts JA, Richardson JD, Chowdhury EA, Holman GD, Tsintzas K, Thompson D. The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults. Am J Clin Nutr. 2014 Aug;100(2):539-47. doi: 10.3945/ajcn.114.083402. Epub 2014 Jun 4.</citation>
    <PMID>24898233</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>March 5, 2019</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 15, 2023</last_update_submitted>
  <last_update_submitted_qc>April 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bath</investigator_affiliation>
    <investigator_full_name>James Betts</investigator_full_name>
    <investigator_title>Professor James Betts</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04417205
org study id: DC-I
nct id: NCT04417205
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Following the establishment of causal links between breakfast consumption, the individual
      components of energy balance, and health it is now important to examine and target the
      underlying biological mechanisms involved to maximise potential health benefits.

      To begin investigating the outlined mechanisms healthy, non-obese participants will be
      recruited to take part in phase I (acute design) of a wider project.
Causal links between breakfast consumption, the individual components of energy balance, and
      health have recently been established and it is now important to examine and target the
      underlying biological mechanisms over a longer period of time to maximise potential health
      benefits.

      Specifically, the substitution of a portion of carbohydrate for protein at breakfast may
      enhance the potential health benefits of breakfast through targeting distinct mechanistic
      pathways. Broadly, introducing a greater protein load at breakfast increases insulin
      secretion and delays gastric emptying, thereby eliciting a potentiated insulin response. In
      turn this may therefore improve glucose tolerance during a subsequent meal. Additionally,
      maintenance of euglycaemia following breakfast consumption, coupled with the thermic effect
      of feeding protein may accentuate the elevated energy expenditure following breakfast
      observed in previous studies. Finally, both the physical and chemical properties of protein
      exert a marked satiating effect. Collectively, these mechanisms could interact to maximise
      the net impact of breakfast on energy balance and associated health outcomes. However, whilst
      the evidence indicates obvious benefits of feeding a higher protein dose at breakfast,
      relatively little research has focused on the response to protein over multiple meals/days.
      Furthermore, and importantly, the mechanisms involved in the second-meal phenomenon and the
      potential for initial meals of varied composition to target these mechanisms have never been
      systematically investigated.

      To begin investigating the outlined mechanisms healthy, non-obese participants will be
      recruited to undergo a 4 week intervention study in which they will consume one of three
      breakfasts for 28-days. The breakfast interventions provide will be:

      Carbohydrate rich breakfast

      Whey protein enriched breakfast

      Extended morning fast

      Participants will undergo 7 days of habitual physical activity and diet monitoring prior to
      visiting the laboratory for their preliminary metabolic assessment in which they will consume
      the carbohydrate rich breakfast followed by an ad libitum meal for lunch. They will then be
      randomised to one of the 3 breakfast interventions for 28-days. During the 28-days weekly
      monitoring of physical activity and energy intake will take place in order to assess energy
      balance.

      Upon completion of the intervention phase participants will revisit the laboratory to
      replicate the initial visit in which postprandial metabolism was assessed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomised to one of 3 intervention arms.
primary purpose: Basic Science
masking: Single (Participant)
masking description: Where applicable (i.e. the two breakfast feeding interventions) participants will be blinded to the breakfast that they receive for 28-days.
measure: Change in physical activity thermogenesis
time frame: Assessed for 1 week at baseline, 3 days a week during weeks 1-3 of the intervention and again for 1 week in the 4th week of the intervention.
description: Energy expenditure measured using physical activity monitor
measure: Change in expression of circadian clock genes measured in whole blood
time frame: Baseline and 4-weeks
description: Pre and post intervention change clock gene expression
measure: Change in postprandial glycaemia following carbohydrate rich test breakfast and lunch over 4 weeks
time frame: Baseline and 4-weeks
description: The postprandial time course response of plasma glucose to the test breakfast and lunch meals
measure: Change in postprandial insulinaemia following carbohydrate rich test breakfast and lunch over 4 weeks
time frame: Assessed at baseline and after 4 weeks of the intervention
description: The postprandial time course response of plasma insulin to the test breakfast and lunch meals
measure: Change in body mass
time frame: 4 weeks
description: Participants will be weighed prior to the intervention and again upon completion
measure: Change in postprandial incretin hormone response following breakfast and lunch
time frame: Baseline and 4 weeks
description: The postprandial time course response of plasma incretin hormones (e.g. GLP-1 & GIP) to the the test breakfast.
measure: Change in subjective appetite ratings following breakfast and lunch
time frame: Baseline and 4 weeks
description: Ratings of appetite provided on subjective appetite scales (on a scale of 0-100 mm where 0 is associated with lower ratings and 100 with higher ratings) following the test breakfast and lunch
measure: Change in fuel oxidation during the test breakfast
time frame: Baseline and 4 weeks
description: Fat and carbohydrate oxidation following breakfast
arm group label: Carbohydrate rich breakfast
arm group type: Active Comparator
description: Participants will be provided with 28-days worth of pre-weighed carbohydrate rich breakfast materials to consume before 1000h daily.
arm group label: Whey protein enriched breakfast
arm group type: Experimental
description: Participants will be provided with 28-days worth of pre-weighed whey protein enriched rich breakfast materials to consume before 1000h daily.
arm group label: Extended morning fast
arm group type: No Intervention
description: Participants will be asked to remain fasted (i.e. to not consume breakfast) until 1200h daily for 28-days.
intervention type: Other
intervention name: Carbohydrate Rich Breakfast
description: Participants will be asked to consume the provided carbohydrate rich breakfast before 1000h daily for 28 days.
arm group label: Carbohydrate rich breakfast
intervention type: Dietary Supplement
intervention name: Whey protein enriched breakfast
description: Participants will be asked to consume the provided whey protein enriched breakfast before 1000h daily for 28 days.
arm group label: Whey protein enriched breakfast
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Harry A Smith, MSci
role: Principal Investigator
affiliation: University of Bath
last name: James A Betts, PhD
role: Principal Investigator
affiliation: University of Bath
facility: 
country: United Kingdom
citation: Leidy HJ, Ortinau LC, Douglas SM, Hoertel HA. Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, "breakfast-skipping," late-adolescent girls. Am J Clin Nutr. 2013 Apr;97(4):677-88. doi: 10.3945/ajcn.112.053116. Epub 2013 Feb 27.
PMID: 23446906
citation: Bray GA, Redman LM, de Jonge L, Covington J, Rood J, Brock C, Mancuso S, Martin CK, Smith SR. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber. Am J Clin Nutr. 2015 Mar;101(3):496-505. doi: 10.3945/ajcn.114.091769. Epub 2015 Jan 14.
PMID: 25733634
citation: Park YM, Heden TD, Liu Y, Nyhoff LM, Thyfault JP, Leidy HJ, Kanaley JA. A high-protein breakfast induces greater insulin and glucose-dependent insulinotropic peptide responses to a subsequent lunch meal in individuals with type 2 diabetes. J Nutr. 2015 Mar;145(3):452-8. doi: 10.3945/jn.114.202549. Epub 2014 Dec 24.
PMID: 25733459
citation: Chowdhury EA, Richardson JD, Holman GD, Tsintzas K, Thompson D, Betts JA. The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults. Am J Clin Nutr. 2016 Mar;103(3):747-56. doi: 10.3945/ajcn.115.122044. Epub 2016 Feb 10.
PMID: 26864365
citation: Betts JA, Richardson JD, Chowdhury EA, Holman GD, Tsintzas K, Thompson D. The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults. Am J Clin Nutr. 2014 Aug;100(2):539-47. doi: 10.3945/ajcn.114.083402. Epub 2014 Jun 4.
PMID: 24898233
responsible party type: Principal Investigator
investigator affiliation: University of Bath
investigator full name: James Betts
investigator title: Professor James Betts
mesh term: Weight Loss
sharing ipd: Undecided