<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/NCT03819972</url>
  </required_header>
  <id_info>
    <org_study_id>PROCAL-JW</org_study_id>
    <nct_id>NCT03819972</nct_id>
  </id_info>
  <brief_title>The Dose Response of Calcium Co-ingested With Protein on GLP-1 Concentrations</brief_title>
  <acronym>PROCAL</acronym>
  <official_title>The Dose Response of Milk Minerals High in Calcium With Protein on Plasma Glucagon-Like Peptide-1 Concentrations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bath</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Arla Foods</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>
      Hormones that are produced by our stomach and intestines play a role in regulating our&#xD;
      appetite and health. One of the most important hormones is called GLP-1. The food we eat&#xD;
      influences the release of this hormone and evidence suggests that protein and calcium are key&#xD;
      nutrients that stimulate the secretion of GLP-1. We want to know if there is a dose related&#xD;
      response by increasing the amount of calcium ingested with a constant amount of protein on&#xD;
      the release of this hormone. We hypothesise that with increasing calcium dose we will see an&#xD;
      increase in GLP-1 concentrations in a curvilinear pattern. This may have benefits for&#xD;
      prescribing an optimal dose of calcium for weight maintenance and health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent work at the University of Bath has shown that when ingested with 50 g whey protein&#xD;
      hydrolysate, Capolac® (milk minerals high in calcium) potently stimulates availability of the&#xD;
      important hormone glucagon-like peptide-1 (GLP-1). However, it is currently unknown as to&#xD;
      whether there is a dose dependent response to calcium co-ingestion with protein. Therefore we&#xD;
      aim to perform a study on the effect of co-ingesting different doses of Capolac® with 25 g&#xD;
      whey protein hydrolysate on GLP-1 availability. This project will help identify the calcium&#xD;
      dose required with a moderate amount of protein to optimise GLP-1 availability and also&#xD;
      provide insight into whether this may affect food intake and appetite.&#xD;
&#xD;
      Twenty metabolically healthy men and women, age 18-65 years, BMI between 25 and 34.9 kg/m2&#xD;
      will be recruited to participate in a randomised crossover study. Each participant will&#xD;
      undergo 4 trials. Each trial will last ~4 hours and will be separated by a minimum of 48h:&#xD;
&#xD;
        1. CONTROL - 25 g whey protein hydrolysate (227 mg of total calcium ingested)&#xD;
&#xD;
        2. DOSE 1 - 25 g whey protein hydrolysate + 3179 mg Capolac (984 mg of total calcium&#xD;
           ingested)&#xD;
&#xD;
        3. DOSE 2 - 25 g whey protein hydrolysate + 6363 mg Capolac (1742 mg of total calcium&#xD;
           ingested)&#xD;
&#xD;
        4. DOSE 3 - 25 g whey protein hydrolysate + 9547 mg Capolac (2500 mg of total calcium&#xD;
           ingested) Each of these drinks will also contain 500 mL of water and low calorie&#xD;
           sweetener (80 mg sucralose).&#xD;
&#xD;
      Participants will be asked to arrive to the laboratory between 08:00 and 9:00 am after not&#xD;
      eating for between 10-14 hours i.e. in a fasted state (water intake is permitted and&#xD;
      encouraged). Upon arrival at the laboratory a trained phlebotomist staff member will insert a&#xD;
      cannula (a small plastic tube) into a vein in the back of the hand. Participants will then be&#xD;
      given one of the four test drinks, which once ingested will initiate the trial. Just after&#xD;
      the ingestion of the test drink we will ask you to fill out a palatability scale.&#xD;
&#xD;
      Blood samples will be taken at baseline, and at 15, 30, 45, 60, 90, 120 and 180 minutes after&#xD;
      ingestion of the test drink. An appetite questionnaire will also be completed at baseline and&#xD;
      every 60 minutes after ingestion of the test drink to assess appetite sensations. After the&#xD;
      180-minute time point participants will be asked to consume a lunch meal until they are&#xD;
      comfortably full. Once satisfied with the lunch meal they will fill out the final appetite&#xD;
      questionnaire. The trial day will then be complete. Following study completion participants&#xD;
      will be asked to complete a restrained eating questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2019</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 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>
    <intervention_model_description>There are 4 conditions where participants will ingest differing amounts of calcium in a randomised order</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Participant will not be told which drink they will ingest until the end of the study.&#xD;
Individuals not collaborating on the study will randomise the drink order and make up the drinks so the investigator is blinded to which drink the particpant will ingest.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Total plasma glucagon-like peptide-1 concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Active plasma glucagon-like peptide-1 concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma insulin concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma NEFA concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma albumin concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum calcium concentrations</measure>
    <time_frame>4 hours</time_frame>
    <description>Blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective appetite</measure>
    <time_frame>4 hours</time_frame>
    <description>Visual appetite scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ad libitum food intake</measure>
    <time_frame>4 hours</time_frame>
    <description>lunch meal</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>GLP-1 Concentration</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will ingest a drink containing 25 g whey protein hydrolysate (227 mg of total calcium ingested)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will ingest a drink containing 25 g whey protein hydrolysate and 3179 mg Capolac (984 mg of total calcium ingested)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will ingest a drink containing 25 g whey protein hydrolysate and 6363 mg Capolac (1742 mg of total calcium ingested)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will ingest a drink containing 25 g whey protein hydrolysate and 9547 mg Capolac (2500 mg of total calcium ingested)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Dose response of Capolac®</intervention_name>
    <description>Capolac® (milk minerals high in calcium) dose is manipulated</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_label>Dose 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index 25.0-34.9 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;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergies or adverse reactions to calcium or milk proteins.&#xD;
&#xD;
          -  Contradictions to a high intake of calcium e.g. history of kidney stones&#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&#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>
  <location>
    <facility>
      <name>Department for Health, 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>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bath</investigator_affiliation>
    <investigator_full_name>Jonathan Watkins</investigator_full_name>
    <investigator_title>PhD Student</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/NCT03819972
org study id: PROCAL-JW
nct id: NCT03819972
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Hormones that are produced by our stomach and intestines play a role in regulating our
      appetite and health. One of the most important hormones is called GLP-1. The food we eat
      influences the release of this hormone and evidence suggests that protein and calcium are key
      nutrients that stimulate the secretion of GLP-1. We want to know if there is a dose related
      response by increasing the amount of calcium ingested with a constant amount of protein on
      the release of this hormone. We hypothesise that with increasing calcium dose we will see an
      increase in GLP-1 concentrations in a curvilinear pattern. This may have benefits for
      prescribing an optimal dose of calcium for weight maintenance and health.
Recent work at the University of Bath has shown that when ingested with 50 g whey protein
      hydrolysate, Capolac® (milk minerals high in calcium) potently stimulates availability of the
      important hormone glucagon-like peptide-1 (GLP-1). However, it is currently unknown as to
      whether there is a dose dependent response to calcium co-ingestion with protein. Therefore we
      aim to perform a study on the effect of co-ingesting different doses of Capolac® with 25 g
      whey protein hydrolysate on GLP-1 availability. This project will help identify the calcium
      dose required with a moderate amount of protein to optimise GLP-1 availability and also
      provide insight into whether this may affect food intake and appetite.

      Twenty metabolically healthy men and women, age 18-65 years, BMI between 25 and 34.9 kg/m2
      will be recruited to participate in a randomised crossover study. Each participant will
      undergo 4 trials. Each trial will last ~4 hours and will be separated by a minimum of 48h:

        1. CONTROL - 25 g whey protein hydrolysate (227 mg of total calcium ingested)

        2. DOSE 1 - 25 g whey protein hydrolysate + 3179 mg Capolac (984 mg of total calcium
           ingested)

        3. DOSE 2 - 25 g whey protein hydrolysate + 6363 mg Capolac (1742 mg of total calcium
           ingested)

        4. DOSE 3 - 25 g whey protein hydrolysate + 9547 mg Capolac (2500 mg of total calcium
           ingested) Each of these drinks will also contain 500 mL of water and low calorie
           sweetener (80 mg sucralose).

      Participants will be asked to arrive to the laboratory between 08:00 and 9:00 am after not
      eating for between 10-14 hours i.e. in a fasted state (water intake is permitted and
      encouraged). Upon arrival at the laboratory a trained phlebotomist staff member will insert a
      cannula (a small plastic tube) into a vein in the back of the hand. Participants will then be
      given one of the four test drinks, which once ingested will initiate the trial. Just after
      the ingestion of the test drink we will ask you to fill out a palatability scale.

      Blood samples will be taken at baseline, and at 15, 30, 45, 60, 90, 120 and 180 minutes after
      ingestion of the test drink. An appetite questionnaire will also be completed at baseline and
      every 60 minutes after ingestion of the test drink to assess appetite sensations. After the
      180-minute time point participants will be asked to consume a lunch meal until they are
      comfortably full. Once satisfied with the lunch meal they will fill out the final appetite
      questionnaire. The trial day will then be complete. Following study completion participants
      will be asked to complete a restrained eating questionnaire.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: There are 4 conditions where participants will ingest differing amounts of calcium in a randomised order
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: Participant will not be told which drink they will ingest until the end of the study.
Individuals not collaborating on the study will randomise the drink order and make up the drinks so the investigator is blinded to which drink the particpant will ingest.
measure: Total plasma glucagon-like peptide-1 concentrations
time frame: 4 hours
description: Blood sampling
measure: Active plasma glucagon-like peptide-1 concentrations
time frame: 4 hours
description: Blood sampling
measure: Plasma insulin concentrations
time frame: 4 hours
description: Blood sampling
measure: Plasma NEFA concentrations
time frame: 4 hours
description: Blood sampling
measure: Plasma albumin concentrations
time frame: 4 hours
description: Blood sampling
measure: Serum calcium concentrations
time frame: 4 hours
description: Blood sampling
measure: Subjective appetite
time frame: 4 hours
description: Visual appetite scales
measure: ad libitum food intake
time frame: 4 hours
description: lunch meal
arm group label: Control
arm group type: Placebo Comparator
description: Participants will ingest a drink containing 25 g whey protein hydrolysate (227 mg of total calcium ingested)
arm group label: Dose 1
arm group type: Active Comparator
description: Participants will ingest a drink containing 25 g whey protein hydrolysate and 3179 mg Capolac (984 mg of total calcium ingested)
arm group label: Dose 2
arm group type: Active Comparator
description: Participants will ingest a drink containing 25 g whey protein hydrolysate and 6363 mg Capolac (1742 mg of total calcium ingested)
arm group label: Dose 3
arm group type: Active Comparator
description: Participants will ingest a drink containing 25 g whey protein hydrolysate and 9547 mg Capolac (2500 mg of total calcium ingested)
intervention type: Dietary Supplement
intervention name: Dose response of Capolac®
description: Capolac® (milk minerals high in calcium) dose is manipulated
arm group label: Control
arm group label: Dose 1
arm group label: Dose 2
arm group label: Dose 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Bath
investigator full name: Jonathan Watkins
investigator title: PhD Student
sharing ipd: No