<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/NCT03279211</url>
  </required_header>
  <id_info>
    <org_study_id>PROTEOS</org_study_id>
    <nct_id>NCT03279211</nct_id>
  </id_info>
  <brief_title>Amino Acid Digestibility of Whey and Zein Proteins</brief_title>
  <official_title>True Ileal Amino Acid Digestibility of Whey and Zein Proteins in Healthy Volunteers With Naso-ileal Tubes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement</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 main goal of the study is to determine true ileal amino acid digestibility of whey&#xD;
      protein isolate (WPI) and zein proteins in healthy subjects equipped with naso-ileal tube.&#xD;
      The endogenous losses of proteins and amino acids will be determined by collecting digesta&#xD;
      samples after a protein-free diet in a third group of subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      True ileal amino acid digestibility of whey protein isolate (WPI) and zein proteins will be&#xD;
      determined in healthy subjects. The endogenous losses of proteins and amino acids will be&#xD;
      determined by collecting digesta samples after a protein-free test-meal in a different group&#xD;
      of subjects.&#xD;
&#xD;
      24 volunteers will be included in the study (men and women; aged 18-65 y; BMI 18-30 kg/m2)&#xD;
      and tested at AgroParisTech (Human Nutrition Research Centre of Avicenne Hospital). Due to&#xD;
      the invasive procedure of intubation, each volunteer will test only one test-meal (n=8 /&#xD;
      test-meal).&#xD;
&#xD;
      One week before the experiment, the volunteers will follow a standard diet adapted to their&#xD;
      body weight to control their protein intake (1.3 g protein/kg body weight). The volunteers&#xD;
      will arrive at the hospital the morning before the day of the experiment and will be equipped&#xD;
      with a double lumen intestinal tube that will be allowed to progress through the intestinal&#xD;
      tract for 24h. On the day of the experiment, the position of the tube will be checked by&#xD;
      radiography to verify its location at the terminal ileum. A catheter will be inserted in the&#xD;
      forearm vein for blood sampling. A perfusion of the non-absorbable marker polyethylene glycol&#xD;
      -4000 will start to estimate the intestinal flow and the basal ileal sample will be collected&#xD;
      during 30 min. Basal plasma sample will be collected. Then, at t=0, the volunteer will drink&#xD;
      the test-meal. Until t=9h, intestinal content will be continuously collected by aspiration&#xD;
      and pooled every 30 minutes. Blood will be sampled every 30 minutes during 4h and hourly&#xD;
      thereafter.&#xD;
&#xD;
      The test meal will consist of a protein-free biscuit (160 g) and a drink (500 ml) with the&#xD;
      test protein as the sole source of protein or no protein for the protein-free group. Celite&#xD;
      will be added to the protein-free biscuit and inulin labelled with carbon 13 will be added to&#xD;
      the drink as indigestible markers of the meal to allow correction for incomplete collection&#xD;
      of digesta. The test proteins will be WPI or zein.&#xD;
&#xD;
      The total nitrogen will be measured in meal and digesta samples by the coupling of Elemental&#xD;
      Analysis with stable Isotope Ratio Mass Spectrometry (EA-IRMS) and the amino acid&#xD;
      concentration in meal, digesta and plasma samples will be measured by High Performance Liquid&#xD;
      Chromatography (HPLC) in order to determine the ileal bioavailability of amino acid of zein&#xD;
      and whey protein. Plasma hormonal profile will also be determined to evaluate the effect of&#xD;
      each protein sources on metabolic hormones such as insulin, glucagon, leptin, etc.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">December 20, 2019</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>3 groups, one for each protein sources (zein and whey) and one for determination of endogenous amino acid losses (protein-free meal)</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of the concentration of amino acids from dietary sources (whey or zein) in the ileal digesta collected during 9 hours after meal intake to calculate the digestibility of amino acids from whey or zein protein sources.</measure>
    <time_frame>Hour 0 to 9 after intake</time_frame>
    <description>The quantity of amino acids will be determined by HPLC in the ileal digesta collected thanks to the naso-ileal tube during 9 hours after the meal intake. The obligatory endogenous amino acid losses will be estimated by determination of the amino acid content of ileal digesta after intake of the protein-free meal and this value will be subtracted to the values obtained after intake of protein meal to evaluate the quantity of amino acid which comes from dietary sources. Recovery of the indigestible markers (13C-inulin and celite) will allow correction for incomplete collection of digesta.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of the metabolic hormones plasma profile after zein or whey protein intake</measure>
    <time_frame>Hour 0 to 9 after intake</time_frame>
    <description>Blood will be collected hourly during the 9 hours following the intake of the meal containing zein or whey protein. The profile of concentration of metabolic hormones (amylin, C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide 1, glucagon, interleukin -6, insulin, leptin, pancreatic polypeptide, polypeptide tyrosine tyrosine , tumor necrosis factor -α) in plasma will be determined by multiplex hormones assays kit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of the effect of zein and whey protein on glucose homeostasis</measure>
    <time_frame>From the evening before the administration to 9 h after the meal.</time_frame>
    <description>Subjects are administered oral deuterated water the day before the investigation. Gluconeogenesis is assessed by measuring deuterium enrichment in body water and on C5 glucose position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of the effect of zein and whey protein on amino acid plasma concentration</measure>
    <time_frame>From the evening before the administration to 9 h after the meal.</time_frame>
    <description>Blood will be collected hourly during the 9 hours following the intake of the meal containing zein or whey protein. The profile of concentration of amino acids in plasma will be determined by ultra high performance liquid chromatography.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Amino Acid</condition>
  <arm_group>
    <arm_group_label>Zein protein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Zein protein included in the test-meal, 30 g of zein in 500 ml (water + flavour/sugar)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whey protein isolate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Whey protein isolate included in the test-meal, 30 g of zein in 500 ml (water + flavour/sugar)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Protein-free</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>No protein added in the test-meal, only 500 ml of water + flavour/sugar In order to determine the endogenous loss of amino acid in the digesta samples.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whey Protein Isolate 894 Fonterra</intervention_name>
    <description>30 g of protein powder diluted in water</description>
    <arm_group_label>Whey protein isolate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Zein Sigma-Aldrich W555025</intervention_name>
    <description>30 g of protein powder diluted in water</description>
    <arm_group_label>Zein protein</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Protein-free test-meal</intervention_name>
    <description>No protein included in the drink made of water and flavour/sugar</description>
    <arm_group_label>Protein-free</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normal body weight (18 &lt; BMI &lt; 30 kg.m-2)&#xD;
&#xD;
          -  Women or men&#xD;
&#xD;
          -  18 - 65 y&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
          -  Insured under the French social security system&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  For women: use of birth control&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  People under trusteeship&#xD;
&#xD;
          -  Latex, cow milk or corn allergy A&#xD;
&#xD;
          -  HIV, hepatite C virus antibodies, hepatite B virus surface antigen and core antibodies&#xD;
             positive&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Excessive alcohol drinking or drugs intake&#xD;
&#xD;
          -  Hypertension, diabetes, digestive tract, liver or renal diseases, severe heart disease&#xD;
&#xD;
          -  High sport practicing (&gt; 7h/week)&#xD;
&#xD;
          -  Blood donation in the 3 months prior to the study&#xD;
&#xD;
          -  Participation in a clinical study in the 3 months prior to the study&#xD;
&#xD;
          -  No signed informed consent&#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>CRNH Ile de France</name>
      <address>
        <city>Bobigny</city>
        <zip>93900</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>May 31, 2022</last_update_submitted>
  <last_update_submitted_qc>May 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement</investigator_affiliation>
    <investigator_full_name>Robert Benamouzig</investigator_full_name>
    <investigator_title>Professor, Clinical Head of Gastroenterology</investigator_title>
  </responsible_party>
  <keyword>digestibility</keyword>
  <keyword>whey protein</keyword>
  <keyword>zein</keyword>
  <keyword>bioavailability</keyword>
  <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/NCT03279211
org study id: PROTEOS
nct id: NCT03279211
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main goal of the study is to determine true ileal amino acid digestibility of whey
      protein isolate (WPI) and zein proteins in healthy subjects equipped with naso-ileal tube.
      The endogenous losses of proteins and amino acids will be determined by collecting digesta
      samples after a protein-free diet in a third group of subjects.
True ileal amino acid digestibility of whey protein isolate (WPI) and zein proteins will be
      determined in healthy subjects. The endogenous losses of proteins and amino acids will be
      determined by collecting digesta samples after a protein-free test-meal in a different group
      of subjects.

      24 volunteers will be included in the study (men and women; aged 18-65 y; BMI 18-30 kg/m2)
      and tested at AgroParisTech (Human Nutrition Research Centre of Avicenne Hospital). Due to
      the invasive procedure of intubation, each volunteer will test only one test-meal (n=8 /
      test-meal).

      One week before the experiment, the volunteers will follow a standard diet adapted to their
      body weight to control their protein intake (1.3 g protein/kg body weight). The volunteers
      will arrive at the hospital the morning before the day of the experiment and will be equipped
      with a double lumen intestinal tube that will be allowed to progress through the intestinal
      tract for 24h. On the day of the experiment, the position of the tube will be checked by
      radiography to verify its location at the terminal ileum. A catheter will be inserted in the
      forearm vein for blood sampling. A perfusion of the non-absorbable marker polyethylene glycol
      -4000 will start to estimate the intestinal flow and the basal ileal sample will be collected
      during 30 min. Basal plasma sample will be collected. Then, at t=0, the volunteer will drink
      the test-meal. Until t=9h, intestinal content will be continuously collected by aspiration
      and pooled every 30 minutes. Blood will be sampled every 30 minutes during 4h and hourly
      thereafter.

      The test meal will consist of a protein-free biscuit (160 g) and a drink (500 ml) with the
      test protein as the sole source of protein or no protein for the protein-free group. Celite
      will be added to the protein-free biscuit and inulin labelled with carbon 13 will be added to
      the drink as indigestible markers of the meal to allow correction for incomplete collection
      of digesta. The test proteins will be WPI or zein.

      The total nitrogen will be measured in meal and digesta samples by the coupling of Elemental
      Analysis with stable Isotope Ratio Mass Spectrometry (EA-IRMS) and the amino acid
      concentration in meal, digesta and plasma samples will be measured by High Performance Liquid
      Chromatography (HPLC) in order to determine the ileal bioavailability of amino acid of zein
      and whey protein. Plasma hormonal profile will also be determined to evaluate the effect of
      each protein sources on metabolic hormones such as insulin, glucagon, leptin, etc.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 3 groups, one for each protein sources (zein and whey) and one for determination of endogenous amino acid losses (protein-free meal)
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Determination of the concentration of amino acids from dietary sources (whey or zein) in the ileal digesta collected during 9 hours after meal intake to calculate the digestibility of amino acids from whey or zein protein sources.
time frame: Hour 0 to 9 after intake
description: The quantity of amino acids will be determined by HPLC in the ileal digesta collected thanks to the naso-ileal tube during 9 hours after the meal intake. The obligatory endogenous amino acid losses will be estimated by determination of the amino acid content of ileal digesta after intake of the protein-free meal and this value will be subtracted to the values obtained after intake of protein meal to evaluate the quantity of amino acid which comes from dietary sources. Recovery of the indigestible markers (13C-inulin and celite) will allow correction for incomplete collection of digesta.
measure: Determination of the metabolic hormones plasma profile after zein or whey protein intake
time frame: Hour 0 to 9 after intake
description: Blood will be collected hourly during the 9 hours following the intake of the meal containing zein or whey protein. The profile of concentration of metabolic hormones (amylin, C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide 1, glucagon, interleukin -6, insulin, leptin, pancreatic polypeptide, polypeptide tyrosine tyrosine , tumor necrosis factor -α) in plasma will be determined by multiplex hormones assays kit.
measure: Determination of the effect of zein and whey protein on glucose homeostasis
time frame: From the evening before the administration to 9 h after the meal.
description: Subjects are administered oral deuterated water the day before the investigation. Gluconeogenesis is assessed by measuring deuterium enrichment in body water and on C5 glucose position.
measure: Determination of the effect of zein and whey protein on amino acid plasma concentration
time frame: From the evening before the administration to 9 h after the meal.
description: Blood will be collected hourly during the 9 hours following the intake of the meal containing zein or whey protein. The profile of concentration of amino acids in plasma will be determined by ultra high performance liquid chromatography.
arm group label: Zein protein
arm group type: Experimental
description: Zein protein included in the test-meal, 30 g of zein in 500 ml (water + flavour/sugar)
arm group label: Whey protein isolate
arm group type: Experimental
description: Whey protein isolate included in the test-meal, 30 g of zein in 500 ml (water + flavour/sugar)
arm group label: Protein-free
arm group type: Other
description: No protein added in the test-meal, only 500 ml of water + flavour/sugar In order to determine the endogenous loss of amino acid in the digesta samples.
intervention type: Other
intervention name: Whey Protein Isolate 894 Fonterra
description: 30 g of protein powder diluted in water
arm group label: Whey protein isolate
intervention type: Other
intervention name: Zein Sigma-Aldrich W555025
description: 30 g of protein powder diluted in water
arm group label: Zein protein
intervention type: Other
intervention name: Protein-free test-meal
description: No protein included in the drink made of water and flavour/sugar
arm group label: Protein-free
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: France
responsible party type: Principal Investigator
investigator affiliation: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
investigator full name: Robert Benamouzig
investigator title: Professor, Clinical Head of Gastroenterology
sharing ipd: Undecided