<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/NCT03777826</url>
  </required_header>
  <id_info>
    <org_study_id>MPR16TA09791</org_study_id>
    <nct_id>NCT03777826</nct_id>
  </id_info>
  <brief_title>Effects of Synergy on Nutrient Intake and Acceptability in Phenylketonuria (PKU)</brief_title>
  <acronym>ESSENTIAL</acronym>
  <official_title>An Open-label, Explorative, Post Launch, Multicenter, Multi-country Intervention Study of PKU Synergy (an Amino-acid Mixture) to Evaluate Change in Nutrient Intake in PKU Subjects With an Increased Phe-tolerance/Intake</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nutricia Research</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nutricia Research</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>
      Phenylketonuria (PKU) is a rare inherited metabolic disorder, where subjects are born with a&#xD;
      genetic deficiency in the phenylalanine hydroxylase enzyme (PAH), which leaves them unable to&#xD;
      convert Phenylalanine (Phe) into Tyrosine (Tyr). Patients with mild PKU or partly responsive&#xD;
      to the drug synthetic tetrahydrobiopterin (BH4) (Kuvan®) can change to a more relaxed diet.&#xD;
      However due to difficulty to adapt their diet, these patients are at risk of an imbalanced&#xD;
      nutritional status and an insufficient intake of specific micronutrients, essential amino&#xD;
      acids and DHA (Docosahexaenoic acid). The study product is designed to improve the&#xD;
      nutritional status of the patients.&#xD;
&#xD;
      The study investigates if the nutritional status is indeed improved following 24 week use of&#xD;
      the study product, and also the study aims to evaluate product acceptability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 26, 2019</start_date>
  <completion_date type="Actual">May 27, 2021</completion_date>
  <primary_completion_date type="Actual">May 27, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nutrient intake</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change in nutrient intake after 24 weeks by analysis of 3 day diet diary. Nutrients (energy, micronutrients, essential amino acids and DHA) in [(m)/(micro)gram/day] or [mg/day or mg/kg/day]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Product acceptability</measure>
    <time_frame>24 weeks</time_frame>
    <description>Product acceptability questionnaire [category/score] [0-10] and [0-5]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compliance</measure>
    <time_frame>24 weeks</time_frame>
    <description>Compliance (product consumption) using daily product intake diary [number of products used per week; per sachet of 33g]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phenylalanine (Phe) levels</measure>
    <time_frame>24 weeks</time_frame>
    <description>Dried bloodspot Phenylalanine (Phe) levels [µmol/L]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood chemistry: nutritional status</measure>
    <time_frame>24 weeks</time_frame>
    <description>Blood chemistry: levels measured in blood: Full Fatty acid profile [For each FA Erythrocyte Membranes level (%FA)], full Amino acid profile [µmol/L], Vitamin B12 [pM], Vitamin D [ng/ml /nmol/L]; Folic acid [nM]; Selenium [µM]; Iodine [µg/L/ ng/mL]; Calcium [mg/dL]; Zinc [µmol/L]; Iron [µg/L] analyzed in blood samples by central laboratories</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometrics: weight</measure>
    <time_frame>24 weeks</time_frame>
    <description>Anthropometrics: Weight [kg]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometrics: height</measure>
    <time_frame>24 weeks</time_frame>
    <description>Anthropometrics: Height [cm or m]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometrics: BMI</measure>
    <time_frame>24 weeks</time_frame>
    <description>Anthropometrics: BMI [kg/m2], calculated from weight/height</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety Parameters (Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events</description>
  </other_outcome>
  <other_outcome>
    <measure>Tolerance (Standard gastrointestinal questionnaire reporting)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Tolerance: Standard gastrointestinal questionnaire reporting of diarrhea constipation, abdominal distension, nausea, vomiting, burping, flatulence, regurgitation, and colic/cramps (0, 1, 12 and 24 weeks) [absent, mild, moderate, severe]</description>
  </other_outcome>
  <other_outcome>
    <measure>Subject characteristics</measure>
    <time_frame>week 0</time_frame>
    <description>Age [years]&#xD;
Sex [male/female]&#xD;
Country [Germany/Netherlands]</description>
  </other_outcome>
  <other_outcome>
    <measure>Phe tolerance level and/or range</measure>
    <time_frame>week 0</time_frame>
    <description>[mg Phe/day]</description>
  </other_outcome>
  <other_outcome>
    <measure>PKU phenotype</measure>
    <time_frame>week 0</time_frame>
    <description>Recording of PKU (Phenylketonuria) genotype from medical history [hyperphenylalaninemia (HPA) or mild/moderate/classic PKU]</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Phenylketonurias</condition>
  <arm_group>
    <arm_group_label>Open label (1 arm)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Open label use of study product (post-marketing): PKU Synergy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PKU Synergy</intervention_name>
    <description>PKU Synergy is a citrus flavored, powdered amino-acid mixture (containing traces of Phe, 4,3mg per portion; and 20 gr. Protein Equivalent (PE)) with a tailored amino acid and micronutrient profile adapted for the special requirements of HPA/PKU (Hyperphenylalaninemia/Phenylketonuria) subjects over 10 years of age with an increased Phenylalanine-(Phe) tolerance/intake.</description>
    <arm_group_label>Open label (1 arm)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. PKU subjects identified by newborn screening and started low-Phe diet before 3 months&#xD;
             of age&#xD;
&#xD;
          2. PKU subjects (with or without current AAM use) with an increased Phe-tolerance/intake&#xD;
             due to:&#xD;
&#xD;
               -  Mild PKU phenotype&#xD;
&#xD;
               -  BH4 treatment&#xD;
&#xD;
          3. If treated with BH4, PKU subjects should be on a stable BH4 treatment for at least 26&#xD;
             consecutive weeks up to start test product intake&#xD;
&#xD;
          4. Age≥12 years&#xD;
&#xD;
          5. If subjects (irrespective whether BH4 users or mild PKU) use amino-acid mixture(s;&#xD;
             AAM), then a maximum of 25 Protein Equivalents (PE) derived from the AAM per day&#xD;
             applies and usage on a daily basis for at least 26 consecutive weeks up to Visit 1&#xD;
&#xD;
          6. If subjects (irrespective whether BH4 users or mild PKU) use AAMs they should be&#xD;
             capable and willing to substitute their current AAM(s; maximum of 25 PE per day) with&#xD;
             one portion of the test product per day&#xD;
&#xD;
          7. If subjects (irrespective whether BH4 users or mild PKU) use omega-3, antioxidant,&#xD;
             and/or vitamin supplements, to stop usage of the supplements and be able and willing&#xD;
             to substitute with the test product&#xD;
&#xD;
          8. Willing and able to comply with study procedures&#xD;
&#xD;
          9. Willing and able to provide informed consent (and assent in case of minors if required&#xD;
             by local law/regulations)&#xD;
&#xD;
         10. For women of childbearing potential: not to have the intention to become pregnant&#xD;
             during the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. For women: Currently pregnant or lactating&#xD;
&#xD;
          2. Current or prior use of the test product within six weeks prior to entry into the&#xD;
             study&#xD;
&#xD;
          3. Concurrent conditions (including renal failure and severe hepatic failure) and&#xD;
             medication that could interfere with participation, outcome parameters or safety (as&#xD;
             determined by Investigator)&#xD;
&#xD;
          4. Psychotropic medication (i.e. medication affecting the nervous system) and inotropic&#xD;
             medication&#xD;
&#xD;
          5. Any condition creating high risk of poor compliance with study&#xD;
&#xD;
          6. Participation in any other studies involving investigational or marketed products&#xD;
             concomitantly or within six weeks prior to entry into the study. Except for studies&#xD;
             related to Kuvan® (synthetic tetrahydrobiopterin (BH4)) without diagnostic,&#xD;
             therapeutic or experimental intervention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University hospital Leipzig</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University hospital Münster</name>
      <address>
        <city>Münster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen (UMCG)</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>December 8, 2021</last_update_submitted>
  <last_update_submitted_qc>December 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2021</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>
  <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/NCT03777826
org study id: MPR16TA09791
nct id: NCT03777826
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phenylketonuria (PKU) is a rare inherited metabolic disorder, where subjects are born with a
      genetic deficiency in the phenylalanine hydroxylase enzyme (PAH), which leaves them unable to
      convert Phenylalanine (Phe) into Tyrosine (Tyr). Patients with mild PKU or partly responsive
      to the drug synthetic tetrahydrobiopterin (BH4) (Kuvan®) can change to a more relaxed diet.
      However due to difficulty to adapt their diet, these patients are at risk of an imbalanced
      nutritional status and an insufficient intake of specific micronutrients, essential amino
      acids and DHA (Docosahexaenoic acid). The study product is designed to improve the
      nutritional status of the patients.

      The study investigates if the nutritional status is indeed improved following 24 week use of
      the study product, and also the study aims to evaluate product acceptability.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Nutrient intake
time frame: 24 weeks
description: Change in nutrient intake after 24 weeks by analysis of 3 day diet diary. Nutrients (energy, micronutrients, essential amino acids and DHA) in [(m)/(micro)gram/day] or [mg/day or mg/kg/day]
measure: Product acceptability
time frame: 24 weeks
description: Product acceptability questionnaire [category/score] [0-10] and [0-5]
measure: Compliance
time frame: 24 weeks
description: Compliance (product consumption) using daily product intake diary [number of products used per week; per sachet of 33g]
measure: Phenylalanine (Phe) levels
time frame: 24 weeks
description: Dried bloodspot Phenylalanine (Phe) levels [µmol/L]
measure: Blood chemistry: nutritional status
time frame: 24 weeks
description: Blood chemistry: levels measured in blood: Full Fatty acid profile [For each FA Erythrocyte Membranes level (%FA)], full Amino acid profile [µmol/L], Vitamin B12 [pM], Vitamin D [ng/ml /nmol/L]; Folic acid [nM]; Selenium [µM]; Iodine [µg/L/ ng/mL]; Calcium [mg/dL]; Zinc [µmol/L]; Iron [µg/L] analyzed in blood samples by central laboratories
measure: Anthropometrics: weight
time frame: 24 weeks
description: Anthropometrics: Weight [kg]
measure: Anthropometrics: height
time frame: 24 weeks
description: Anthropometrics: Height [cm or m]
measure: Anthropometrics: BMI
time frame: 24 weeks
description: Anthropometrics: BMI [kg/m2], calculated from weight/height
measure: Safety Parameters (Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events)
time frame: 24 weeks
description: Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events
measure: Tolerance (Standard gastrointestinal questionnaire reporting)
time frame: 24 weeks
description: Tolerance: Standard gastrointestinal questionnaire reporting of diarrhea constipation, abdominal distension, nausea, vomiting, burping, flatulence, regurgitation, and colic/cramps (0, 1, 12 and 24 weeks) [absent, mild, moderate, severe]
measure: Subject characteristics
time frame: week 0
description: Age [years]
Sex [male/female]
Country [Germany/Netherlands]
measure: Phe tolerance level and/or range
time frame: week 0
description: [mg Phe/day]
measure: PKU phenotype
time frame: week 0
description: Recording of PKU (Phenylketonuria) genotype from medical history [hyperphenylalaninemia (HPA) or mild/moderate/classic PKU]
arm group label: Open label (1 arm)
arm group type: Other
description: Open label use of study product (post-marketing): PKU Synergy
intervention type: Other
intervention name: PKU Synergy
description: PKU Synergy is a citrus flavored, powdered amino-acid mixture (containing traces of Phe, 4,3mg per portion; and 20 gr. Protein Equivalent (PE)) with a tailored amino acid and micronutrient profile adapted for the special requirements of HPA/PKU (Hyperphenylalaninemia/Phenylketonuria) subjects over 10 years of age with an increased Phenylalanine-(Phe) tolerance/intake.
arm group label: Open label (1 arm)
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Germany
country: Netherlands
responsible party type: Sponsor
mesh term: Phenylketonurias
sharing ipd: No