xml: <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/NCT05971563</url>
    </required_header>
    <id_info>
      <org_study_id>281421</org_study_id>
      <nct_id>NCT05971563</nct_id>
    </id_info>
    <brief_title>Amino Acid Kinetics of GMP-AA in Healthy Human Volunteers</brief_title>
    <official_title>Amino Acid Kinetics of GMP-AA vs. Phenylalanine-free Amino Acids Compared With Natural Protein in Healthy Adults Volunteers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Birmingham Women's and Children's NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Birmingham Women's and Children's NHS Foundation Trust</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>
        Children with phenylketonuria (PKU) are treated with a special diet supplemented with a&#xD;
        synthetic protein based on amino acids. These have a poor taste and are inefficiently used by&#xD;
        the body. A different type of synthetic protein, called glycomacropeptide is being tried in&#xD;
        PKU. It tastes better than amino acids but it requires the addition of some extra amino acids&#xD;
        which may worsen how well it is absorbed compared with traditional amino acid supplements. We&#xD;
        will perform a 3-part trial in healthy adult volunteers to compare amino acids vs&#xD;
        glycomacropeptide protein with a 'normal protein' (casein) to examine the absorption&#xD;
        properties of these proteins. Volunteers will take one dose of each of the protein sources on&#xD;
        3 different days. Blood and urine samples will be collected examining the rate of absorption&#xD;
        of amino acids over 5 hours on each study day.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In the USA, casein glycomacropeptide (CGMP), a low phenylalanine (Phe) 64-amino acid peptide&#xD;
        derived from cheese whey, is widely promoted as a low Phe protein substitute in&#xD;
        phenylketonuria (PKU). Protein substitute is composed of non-essential and essential amino&#xD;
        acids which replace natural protein in the diet in order to enable normal growth and&#xD;
        suppression of blood Phe levels.&#xD;
  &#xD;
        It is suggested that CGMP has a slower absorption than usual protein substitute based on&#xD;
        amino acids only (amino acids-AA). This compositional change may enhance protein utilization&#xD;
        leading to improved blood Phe control. In PKU, any protein substitute that has its absorption&#xD;
        closer to the normal 'physiological state' should be advantageous but pure CGMP is lacking in&#xD;
        several essential and conditionally essential amino acids (e.g. tyrosine, leucine,&#xD;
        tryptophan, histidine). To ensure that CGMP is safe for PKU, it is supplemented with&#xD;
        deficient AA (CGMP-AA). Evidence from 'normal' nutritional research suggests that adding AA&#xD;
        to natural protein (similar to CGMP-AA), worsens rather than improves efficiency of protein&#xD;
        absorption. It is essential to ascertain if CGMP-AA enhances, worsens or has the same&#xD;
        absorption when compared with traditional AA substitutes, particularly when prescribing&#xD;
        CGMP-AA for children and maternal PKU. The investigators aim to perform a three-part,&#xD;
        randomized, controlled, trial in healthy adult volunteers comparing absorption of CGMP-AA&#xD;
        (study product 1) vs. AA (study product 2) vs. normal protein (casein) (study product 3).&#xD;
        After overnight fasting, healthy volunteers will consume a standard dose of each of the study&#xD;
        products. Over the course of 4 hours, plasma AA will be monitored 8 times and this will&#xD;
        provide greater insight into the kinetic absorption of CGMP-AA in PKU. The investigators hope&#xD;
        these results will add to existing safety and efficacy data about using CGMP-AA in PKU.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">October 18, 2022</start_date>
    <completion_date type="Anticipated">August 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2023</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>A three-way, randomized, controlled, open-label, crossover, single-dose clinical trial in healthy adult volunteers.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Total EAA concentrations</measure>
      <time_frame>240 minutes for each protein</time_frame>
      <description>To compare the total EAA concentrations after oral ingestion of one dose of three different protein supplements: cGMP-AA vs. AA only vs. casein.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mean CMAX</measure>
      <time_frame>240 minutes for each protein</time_frame>
      <description>Mean CMAX within 240 minutes of ingestion of each of the 3 proteins</description>
    </primary_outcome>
    <primary_outcome>
      <measure>AUC of EAA's</measure>
      <time_frame>240 minutes for each protein</time_frame>
      <description>AUC of EAA's within 240 minutes of ingestion of each of the 3 proteins</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Curve characteristics (Cmax)</measure>
      <time_frame>240 minutes for each protein</time_frame>
      <description>Curve characteristics (Cmax) of the following quantities:&#xD;
  LNAA;&#xD;
  BCAA;&#xD;
  Total AA;&#xD;
  Tyrosine;&#xD;
  Phenylalanine;&#xD;
  Urea;&#xD;
  Insulin.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Curve characteristics (AUC)</measure>
      <time_frame>240 minutes for each protein</time_frame>
      <description>Curve characteristics (AUC) of the following quantities:&#xD;
  LNAA;&#xD;
  BCAA;&#xD;
  Total AA;&#xD;
  Tyrosine;&#xD;
  Phenylalanine;&#xD;
  Urea;&#xD;
  Insulin.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Phenylketonurias</condition>
    <arm_group>
      <arm_group_label>Casein</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Glycomacropeptide</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>L- amino acids</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Casein</intervention_name>
      <description>Natural protein</description>
      <arm_group_label>Casein</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>L-amino acids</intervention_name>
      <description>Synthetic amino acids based protein substitute for Phenylketonuria</description>
      <arm_group_label>L- amino acids</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>CGMP-AA</intervention_name>
      <description>Glycomacropeptide based protein substitute for Phenylketonuria</description>
      <arm_group_label>Glycomacropeptide</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male and female healthy subjects without PKU;&#xD;
  &#xD;
            -  18 to 50 years of age;&#xD;
  &#xD;
            -  Female subjects with a negative urine pregnancy test prior to entry into the study and&#xD;
               who are practicing an adequate method of birth control during the study;&#xD;
  &#xD;
            -  Good general health status proven by medical history and clinical laboratory values&#xD;
               within normal limits or considered not clinically significant by the investigator;&#xD;
  &#xD;
            -  Non-smokers or not current smokers;&#xD;
  &#xD;
            -  Body mass index (BMI) between 18 and 30 kg/m2 and weight (kg)&#xD;
  &#xD;
            -  No existence of disorders or any comorbidity.&#xD;
  &#xD;
            -  Willing to follow the study protocol and to take the study products;&#xD;
  &#xD;
            -  Able to understand study procedures and sign informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of alcohol or drugs abuse;&#xD;
  &#xD;
            -  Smokers;&#xD;
  &#xD;
            -  Women who are pregnant, breast feeding, or planning to become pregnant during the&#xD;
               course of the study;&#xD;
  &#xD;
            -  Received an investigational drug or device within 30 days (or 5 half-lives, whichever&#xD;
               is longer) of dosing;&#xD;
  &#xD;
            -  Existence of any disorder, food allergy or comorbidity (clinically significant&#xD;
               including gastrointestinal, renal, pulmonary, hepatic, cardiovascular and endocrine&#xD;
               disorders) - to be decided by investigator from medical history;&#xD;
  &#xD;
            -  Current illness or infection that could interfere with the study;&#xD;
  &#xD;
            -  Use of laxatives;&#xD;
  &#xD;
            -  Use of antibiotics in the last 3 months;&#xD;
  &#xD;
            -  Use of medication that could influence protein metabolism (like growth hormone,&#xD;
               anabolic steroids, hormone replacement) - to be judged by the investigator;&#xD;
  &#xD;
            -  Participation in any clinical trial in the last 3 months;&#xD;
  &#xD;
            -  Blood donation within the past 3 months;&#xD;
  &#xD;
            -  On a medically prescribed diet;&#xD;
  &#xD;
            -  Unable to follow the study protocol or provide consent;&#xD;
  &#xD;
            -  Unable to take or tolerate one of the study products.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University Hospitals Birmingham NHS Foundation Trust</name>
        <address>
          <city>Birmingham</city>
          <state>West Midlands</state>
          <zip>B15 2TT</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Phenylketonurias</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Caseins</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>All materials, information (oral or written) and unpublished documentation provided to the Investigators (or any company/institution acting on their behalf), including this protocol and the patient Case Report Forms, are the exclusive property of the Research team and may not be given or disclosed, either in part or in whole, by any person to any third party without the prior express consent of the research team. Potential and recruited patients will be identified by a unique study number with only the local research staff having the corresponding list of full patient identifiers, which should be kept secure. CRFs will be labelled with patient initials and their unique study number. Laboratory results shall be labelled similarly having had patient-identifiable details removed. All unpublished information shall be kept confidential and shall not be published or disclosed to a third party without the prior written consent of the research team.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05971563
  org study id: 281421
  nct id: NCT05971563
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Children with phenylketonuria (PKU) are treated with a special diet supplemented with a
        synthetic protein based on amino acids. These have a poor taste and are inefficiently used by
        the body. A different type of synthetic protein, called glycomacropeptide is being tried in
        PKU. It tastes better than amino acids but it requires the addition of some extra amino acids
        which may worsen how well it is absorbed compared with traditional amino acid supplements. We
        will perform a 3-part trial in healthy adult volunteers to compare amino acids vs
        glycomacropeptide protein with a 'normal protein' (casein) to examine the absorption
        properties of these proteins. Volunteers will take one dose of each of the protein sources on
        3 different days. Blood and urine samples will be collected examining the rate of absorption
        of amino acids over 5 hours on each study day.
  In the USA, casein glycomacropeptide (CGMP), a low phenylalanine (Phe) 64-amino acid peptide
        derived from cheese whey, is widely promoted as a low Phe protein substitute in
        phenylketonuria (PKU). Protein substitute is composed of non-essential and essential amino
        acids which replace natural protein in the diet in order to enable normal growth and
        suppression of blood Phe levels.
  
        It is suggested that CGMP has a slower absorption than usual protein substitute based on
        amino acids only (amino acids-AA). This compositional change may enhance protein utilization
        leading to improved blood Phe control. In PKU, any protein substitute that has its absorption
        closer to the normal 'physiological state' should be advantageous but pure CGMP is lacking in
        several essential and conditionally essential amino acids (e.g. tyrosine, leucine,
        tryptophan, histidine). To ensure that CGMP is safe for PKU, it is supplemented with
        deficient AA (CGMP-AA). Evidence from 'normal' nutritional research suggests that adding AA
        to natural protein (similar to CGMP-AA), worsens rather than improves efficiency of protein
        absorption. It is essential to ascertain if CGMP-AA enhances, worsens or has the same
        absorption when compared with traditional AA substitutes, particularly when prescribing
        CGMP-AA for children and maternal PKU. The investigators aim to perform a three-part,
        randomized, controlled, trial in healthy adult volunteers comparing absorption of CGMP-AA
        (study product 1) vs. AA (study product 2) vs. normal protein (casein) (study product 3).
        After overnight fasting, healthy volunteers will consume a standard dose of each of the study
        products. Over the course of 4 hours, plasma AA will be monitored 8 times and this will
        provide greater insight into the kinetic absorption of CGMP-AA in PKU. The investigators hope
        these results will add to existing safety and efficacy data about using CGMP-AA in PKU.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: A three-way, randomized, controlled, open-label, crossover, single-dose clinical trial in healthy adult volunteers.
  primary purpose: Other
  masking: None (Open Label)
  measure: Total EAA concentrations
  time frame: 240 minutes for each protein
  description: To compare the total EAA concentrations after oral ingestion of one dose of three different protein supplements: cGMP-AA vs. AA only vs. casein.
  measure: Mean CMAX
  time frame: 240 minutes for each protein
  description: Mean CMAX within 240 minutes of ingestion of each of the 3 proteins
  measure: AUC of EAA's
  time frame: 240 minutes for each protein
  description: AUC of EAA's within 240 minutes of ingestion of each of the 3 proteins
  measure: Curve characteristics (Cmax)
  time frame: 240 minutes for each protein
  description: Curve characteristics (Cmax) of the following quantities:
  LNAA;
  BCAA;
  Total AA;
  Tyrosine;
  Phenylalanine;
  Urea;
  Insulin.
  measure: Curve characteristics (AUC)
  time frame: 240 minutes for each protein
  description: Curve characteristics (AUC) of the following quantities:
  LNAA;
  BCAA;
  Total AA;
  Tyrosine;
  Phenylalanine;
  Urea;
  Insulin.
  arm group label: Casein
  arm group type: Active Comparator
  arm group label: Glycomacropeptide
  arm group type: Active Comparator
  arm group label: L- amino acids
  arm group type: Active Comparator
  intervention type: Dietary Supplement
  intervention name: Casein
  description: Natural protein
  arm group label: Casein
  intervention type: Dietary Supplement
  intervention name: L-amino acids
  description: Synthetic amino acids based protein substitute for Phenylketonuria
  arm group label: L- amino acids
  intervention type: Dietary Supplement
  intervention name: CGMP-AA
  description: Glycomacropeptide based protein substitute for Phenylketonuria
  arm group label: Glycomacropeptide
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Phenylketonurias
  mesh term: Caseins
  sharing ipd: No
  ipd description: All materials, information (oral or written) and unpublished documentation provided to the Investigators (or any company/institution acting on their behalf), including this protocol and the patient Case Report Forms, are the exclusive property of the Research team and may not be given or disclosed, either in part or in whole, by any person to any third party without the prior express consent of the research team. Potential and recruited patients will be identified by a unique study number with only the local research staff having the corresponding list of full patient identifiers, which should be kept secure. CRFs will be labelled with patient initials and their unique study number. Laboratory results shall be labelled similarly having had patient-identifiable details removed. All unpublished information shall be kept confidential and shall not be published or disclosed to a third party without the prior written consent of the research team.