<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/NCT03771391</url>
  </required_header>
  <id_info>
    <org_study_id>MCT-W-PKUSp-2017-06-29</org_study_id>
    <secondary_id>F-2018-043</secondary_id>
    <nct_id>NCT03771391</nct_id>
  </id_info>
  <brief_title>A 16 Week Study Evaluating the Introduction of a GMP Based Protein Substitute in Participants With PKU</brief_title>
  <acronym>GMP In PKU</acronym>
  <official_title>Multicentre Study Project to Evaluate the New Generation of Protein Supplements With Glycomacropeptide (GMP) in Patients With Phenylketonuria (PKU) Aged 10 Years and Older Over a 16 Week Period.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vitaflo International, Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kreiskliniken Reutlingen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vitaflo International, Ltd</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>
      This study aims to measure changes in participants' blood phenylalanine (Phe) levels in&#xD;
      participants with PKU when switching from a conventional amino acid based protein substitute&#xD;
      to a GMP based protein substitute (PKU Sphere) over a 16 week period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a stepped wedge, open-label study of PKU Sphere for the dietary management of&#xD;
      participants with Phenylketonuria. It will be carried out with 33 participants who will be&#xD;
      randomised into one of three clusters. The total study length per patient is 16 weeks. Each&#xD;
      cluster transitions from taking their standard amino acid product alone to incorporating PKU&#xD;
      Sphere (at least 50% of their protein substitue requirement) at different timepoints: week 5,&#xD;
      9 or 13.&#xD;
&#xD;
      Participants will have a face-to-face clinical review at the time of recruitment (week 0) and&#xD;
      at 16 weeks (completion of the study). They will also have an additional telephone review&#xD;
      when they switch onto PKU Sphere.&#xD;
&#xD;
      Blood samples will be taken at baseline, and then every two weeks for the duration of the&#xD;
      study.&#xD;
&#xD;
      In addition to these study visits and procedures, routine clinical care will continue in line&#xD;
      with local guidelines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2018</start_date>
  <completion_date type="Actual">July 31, 2023</completion_date>
  <primary_completion_date type="Actual">October 30, 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>The study has a stepped wedge design, which is chosen over the alternative cross-over study as it allows that all participants start on the amino acid supplement and avoids the difficulty of the 'wash-out' period being the same as one of the treatment strategies being offered.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>At the point of randomisation every effort will be made to ensure that participants are unaware of the cluster they are randomised to; this is to help ensure that compliance is not affected by participants knowing when they will start the new treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in blood Phe</measure>
    <time_frame>Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16.</time_frame>
    <description>Change in blood Phe concentrations when switching from an amino acid based protein substitute to a GMP based one (PKU Sphere). A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in blood tyrosine</measure>
    <time_frame>Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16.</time_frame>
    <description>Impact of a GMP based protein substitute on blood tyrosine levels. A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary intake</measure>
    <time_frame>Weeks 1 and 16.</time_frame>
    <description>Compliance with a low protein diet - 3-day food diary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein substitute intake</measure>
    <time_frame>Weeks 1, 4, 8, 12 and 16</time_frame>
    <description>Compliance with the recommended volume of protein substitute - 3-day protein substitute diary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool patterns</measure>
    <time_frame>Weeks 1, 4, 8, 12 and 16</time_frame>
    <description>3-day diary noting stool type (Bristol stool chart).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satiety questionnaire</measure>
    <time_frame>Weeks 1, 4, 8, 12 and 16</time_frame>
    <description>Short questionnaire asking participants to consider their satiety levels over the last 7 days, asking them if it has increased, stayed the same or decreased. Questionnaire validated as part of a bachelor thesis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptance questionnaire</measure>
    <time_frame>Weeks 1, 4, 8, 12 and 16</time_frame>
    <description>Questionnaire to collect information about taste, odour and practicability of the protein substitutes. The questions are answered on a scale of 1 (bad) to 5 or 6 (good). Questionnaire validated as part of a bachelor thesis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal symptoms questionnaire</measure>
    <time_frame>Weeks 1, 4, 8, 12 and 16</time_frame>
    <description>Short questionnaire asking participants to consider their general gastrointestinal health over the previous 7 days. The occurrence of various GI symptoms are given as never, rare, often or always. Questionnaire validated as part of a bachelor thesis.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Phenylketonurias</condition>
  <arm_group>
    <arm_group_label>4 Weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>8 Weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 Weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PKU Sphere</intervention_name>
    <description>PKU sphere is a powdered, low phenylalanine protein substitute containing a balanced mix of casein glycomacropeptide (GMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals and docosahexaenoic acid (DHA). With sugar and sweetener.</description>
    <arm_group_label>12 Weeks</arm_group_label>
    <arm_group_label>4 Weeks</arm_group_label>
    <arm_group_label>8 Weeks</arm_group_label>
    <other_name>GMP</other_name>
    <other_name>Glycomacropeptide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PKU made in neonatal period&#xD;
&#xD;
          -  Treated by a low-phenylalanine diet and necessity of intake of at least one protein&#xD;
             substitute per day&#xD;
&#xD;
          -  Aged 10 years and above&#xD;
&#xD;
          -  Three blood Phe measurements taken within the preceding six months&#xD;
&#xD;
          -  Willing to replace current amino acid based protein substitute with PKU Sphere&#xD;
&#xD;
          -  Ability to take at least 50% of protein requirements as PKU Sphere&#xD;
&#xD;
          -  Ability to comply with the study protocol, in the opinion of the investigator&#xD;
&#xD;
          -  Willingly given, written, informed consent from patient or parent/guardian&#xD;
&#xD;
          -  Willingly given, written assent (if appropriate)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or planning to become pregnant during the study period&#xD;
&#xD;
          -  Participants with atypical PKU (e.g. BH4 deficient)&#xD;
&#xD;
          -  Intake of sapropterin dihydrochloride (Kuvan) in the six weeks prior to recruitment in&#xD;
             the study&#xD;
&#xD;
          -  Patients with soya, milk or fish allergies&#xD;
&#xD;
          -  Any other severe disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Freisinger</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kreiskliniken Reutlingen GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kreiskliniken Reutlingen</name>
      <address>
        <city>Reutlingen</city>
        <state>Baden-Württemberg</state>
        <zip>D-72764</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phenylketonuria</keyword>
  <keyword>PKU</keyword>
  <keyword>Child</keyword>
  <keyword>Children</keyword>
  <keyword>Adult</keyword>
  <keyword>Adults</keyword>
  <keyword>GMP</keyword>
  <keyword>Glycomacropeptide</keyword>
  <keyword>Amino acid mixture</keyword>
  <keyword>Amino acid</keyword>
  <keyword>Protein supplement</keyword>
  <keyword>Protein substitute</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylketonurias</mesh_term>
  </condition_browse>
  <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/NCT03771391
org study id: MCT-W-PKUSp-2017-06-29
secondary id: F-2018-043
nct id: NCT03771391
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to measure changes in participants' blood phenylalanine (Phe) levels in
      participants with PKU when switching from a conventional amino acid based protein substitute
      to a GMP based protein substitute (PKU Sphere) over a 16 week period.
This is a stepped wedge, open-label study of PKU Sphere for the dietary management of
      participants with Phenylketonuria. It will be carried out with 33 participants who will be
      randomised into one of three clusters. The total study length per patient is 16 weeks. Each
      cluster transitions from taking their standard amino acid product alone to incorporating PKU
      Sphere (at least 50% of their protein substitue requirement) at different timepoints: week 5,
      9 or 13.

      Participants will have a face-to-face clinical review at the time of recruitment (week 0) and
      at 16 weeks (completion of the study). They will also have an additional telephone review
      when they switch onto PKU Sphere.

      Blood samples will be taken at baseline, and then every two weeks for the duration of the
      study.

      In addition to these study visits and procedures, routine clinical care will continue in line
      with local guidelines.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study has a stepped wedge design, which is chosen over the alternative cross-over study as it allows that all participants start on the amino acid supplement and avoids the difficulty of the 'wash-out' period being the same as one of the treatment strategies being offered.
primary purpose: Treatment
masking: Single (Participant)
masking description: At the point of randomisation every effort will be made to ensure that participants are unaware of the cluster they are randomised to; this is to help ensure that compliance is not affected by participants knowing when they will start the new treatment.
measure: Change in blood Phe
time frame: Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16.
description: Change in blood Phe concentrations when switching from an amino acid based protein substitute to a GMP based one (PKU Sphere). A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis.
measure: Change in blood tyrosine
time frame: Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16.
description: Impact of a GMP based protein substitute on blood tyrosine levels. A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis.
measure: Dietary intake
time frame: Weeks 1 and 16.
description: Compliance with a low protein diet - 3-day food diary.
measure: Protein substitute intake
time frame: Weeks 1, 4, 8, 12 and 16
description: Compliance with the recommended volume of protein substitute - 3-day protein substitute diary.
measure: Stool patterns
time frame: Weeks 1, 4, 8, 12 and 16
description: 3-day diary noting stool type (Bristol stool chart).
measure: Satiety questionnaire
time frame: Weeks 1, 4, 8, 12 and 16
description: Short questionnaire asking participants to consider their satiety levels over the last 7 days, asking them if it has increased, stayed the same or decreased. Questionnaire validated as part of a bachelor thesis.
measure: Acceptance questionnaire
time frame: Weeks 1, 4, 8, 12 and 16
description: Questionnaire to collect information about taste, odour and practicability of the protein substitutes. The questions are answered on a scale of 1 (bad) to 5 or 6 (good). Questionnaire validated as part of a bachelor thesis.
measure: Gastrointestinal symptoms questionnaire
time frame: Weeks 1, 4, 8, 12 and 16
description: Short questionnaire asking participants to consider their general gastrointestinal health over the previous 7 days. The occurrence of various GI symptoms are given as never, rare, often or always. Questionnaire validated as part of a bachelor thesis.
arm group label: 4 Weeks
arm group type: Experimental
description: All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 4 weeks.
arm group label: 8 Weeks
arm group type: Experimental
description: All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 8 weeks.
arm group label: 12 Weeks
arm group type: Experimental
description: All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 12 weeks.
intervention type: Dietary Supplement
intervention name: PKU Sphere
description: PKU sphere is a powdered, low phenylalanine protein substitute containing a balanced mix of casein glycomacropeptide (GMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals and docosahexaenoic acid (DHA). With sugar and sweetener.
arm group label: 12 Weeks
arm group label: 4 Weeks
arm group label: 8 Weeks
other name: GMP
other name: Glycomacropeptide
criteria: 
gender: All
minimum age: 10 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Freisinger
role: Principal Investigator
affiliation: Kreiskliniken Reutlingen GmbH
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Phenylketonurias
sharing ipd: No