<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/NCT04404530</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00111450</org_study_id>
    <nct_id>NCT04404530</nct_id>
  </id_info>
  <brief_title>Nutritional Impacts of Palynziq on Patients With Phenylketonuria (PKU)</brief_title>
  <official_title>Palynziq and PKU: Treatment Impacts on Diet Quality, Neurological Health, Nutritional Status, and the Metabolome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BioMarin Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phenylketonuria (PKU) is an inherited metabolic disorder that impairs the metabolism of the&#xD;
      essential amino acid phenylalanine (Phe). Without stringent dietary control, Phe accumulates&#xD;
      in the blood and brain of PKU patients, leading to severe cognitive deficits. Achieving&#xD;
      metabolic control, defined as blood Phe levels within the range of 120-360 μmol/L, has been a&#xD;
      significant challenge for PKU patients using traditional diet therapy. The new FDA approved&#xD;
      pharmacologic treatment, Palynziq, offers a new approach that could significantly reduce the&#xD;
      burden of PKU by improving blood Phe levels and allowing for a less restrictive diet. As&#xD;
      little is known about the global metabolic and physiologic effects of Palynziq, the present&#xD;
      study aims to capture changes in diet quality, neurological health, nutritional status, the&#xD;
      nutritional metabolome, and patient perceptions of mental and social health with sustained&#xD;
      Palynziq therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phenylketonuria (PKU) is an autosomal recessive disorder caused by more than 500 pathogenic&#xD;
      variants in the phenylalanine hydroxylase (PAH) gene. Due to these mutations, affected&#xD;
      individuals have reduced activity or complete deficiency of the enzyme phenylalanine&#xD;
      hydroxylase, which metabolizes the essential amino acid phenylalanine (Phe) to tyrosine.&#xD;
      Consequently, Phe and its byproducts accumulate in the blood and brain of PKU patients, which&#xD;
      can have irreparable physical and neurocognitive effects. These may include intellectual&#xD;
      disabilities, seizures, eczema, psychosis, and hypopigmentation. To prevent these adverse&#xD;
      conditions, early diagnosis and meticulous control of blood Phe levels are required. For&#xD;
      optimal metabolic control, the American College of Medical Genetics (ACMG) recommends&#xD;
      lifelong maintenance of Phe concentrations within the range of 120-360 μmol/L.&#xD;
&#xD;
      Diet therapy has dramatically improved metabolic control and nutritional status in PKU&#xD;
      patients and when adherent to dietary treatment, numerous patients have been able to achieve&#xD;
      normal growth and prevent severe cognitive deficits. This, however, is not an easy task given&#xD;
      a steep restriction of intact protein is required to keep blood Phe levels within the&#xD;
      therapeutic range. To meet nutritional needs in the absence of dietary protein, patients&#xD;
      consume large volumes of Phe-free amino acid formulas (medical food) and specialized&#xD;
      low-protein modified foods. While this regimen may improve overall diet quality, due to the&#xD;
      fortification of formula with vitamins and minerals, the poor palatability and high cost&#xD;
      medical food makes diet therapy a significant burden for patients and their families.&#xD;
&#xD;
      Pharmacologic therapies now provide an innovative approach to improve patient health and&#xD;
      quality of life by liberalizing the traditional protein-restricted diet. Palynziq is a&#xD;
      PEGylated recombinant of phenylalanine lyase, which can lower blood Phe concentrations. Given&#xD;
      increasing numbers of PKU patients will be initiating Palynziq therapy, it is essential to&#xD;
      prospectively evaluate the impact of this novel treatment on the neurological health, diet&#xD;
      quality, and nutritional metabolome of patients when administered in a clinical setting. This&#xD;
      knowledge will not only improve the efficacy of the treatment, but will be essential for&#xD;
      expanding the current dietary guidelines to meet the unique needs of patients treated with&#xD;
      Palynziq.&#xD;
&#xD;
      The objectives of this proposal are to obtain information on the diet quality, neurological&#xD;
      health, and nutritional metabolome of patients with PKU at baseline and after intervention&#xD;
      with Palynziq. This is a three-year observational study that includes non-pregnant adults who&#xD;
      have PKU and have obtained a physician's prescription to initiate Palynziq treatment.&#xD;
      Patients who complete three year study are now eligible to participate in a sub study which&#xD;
      extends the main protocol for up to four years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 8, 2019</start_date>
  <completion_date type="Anticipated">November 2027</completion_date>
  <primary_completion_date type="Anticipated">November 2027</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Intra-subject Change in Intact Protein Intake</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Intra-subject change in intact protein intake will be assessed by participant-reported 3-day dietary records.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intra-subject Change in Medical Food Protein Intake</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sub study: Intra-subject change in intact protein and medical food protein intake.</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Average Intact Protein Intake</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Average intact protein intake will be determined by participant-reported 3-day dietary records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days From Palynziq Initiation to Response</measure>
    <time_frame>Baseline up to Response (up to 60 days)</time_frame>
    <description>The average length of time (in days) from Palynziq initiation until response, as defined by three consecutive plasma Phe levels lower than the upper limit of the recommended treatment range (&lt;360 μmol/L) and a significant increase in intact protein intake (at least 60 percent of the dietary reference intake (DRI) or a two-fold increase from baseline diet prescription), will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days From Palynziq Initiation to Consumption of Dietary Reference Intake for Intact Protein</measure>
    <time_frame>Baseline up to 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The average length of time (in days) from Palynziq initiation it takes for participants to consume the dietary reference intake for intact protein (46g females, 56g males).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Neuro-QOL - Cognitive Function - Short Form Score</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The Neuro-QOL Cognitive Function Short Form includes 8 items asking participants about their cognition during the past 7 days. Responses to statements of if cognition problems are occurring are given on a scale from 1 to 5 where 1 = very often and 5 = never. The amount of difficulty experienced from daily life tasks are responded to on a scale from 1 to 5 as 1 = cannot do task and 5 = no difficulty. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more cognition problems than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Neuro-QOL Sleep Disturbance - Short Form Score</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The Neuro-QOL Sleep Disturbance Short Form includes 8 items asking participants about their sleep during the past 7 days. Responses to statements of if sleep problems are occurring are given on a scale from 1 to 5 where 1 = never and 5 = always. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more sleep problems than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The PROMIS Global Health instrument includes 10 items asking participants about their health and quality of life. Responses to items are given on a scale from 1 to 5 where 1 = poor and 5 = excellent. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing greater quality of life than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS-29 Anxiety and Depression Score</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The PROMIS-29 instrument includes 8 items asking participants about anxiety and depression. Responses to are given on a scale from 1 to 5 where 1 = never and 5 = always. The total summed score from these items ranges from 8 to 40 and higher scores indicate greater anxiety and depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS Emotional Support Score</measure>
    <time_frame>Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>The PROMIS Emotional Support instrument includes 16 items asking participants about forms of emotional support they have available. Responses to items are given on a scale from 1 to 5 where 1 = never and 5 = always. Raw scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent has greater emotional support than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Neurotransmitters</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Intra-subject change in neurotransmitter analysis will be assessed using fasting blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Amino Acids</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Intra-subject change in plasma amino acids will be assessed using fasting blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Essential Fatty Acids</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Intra-subject change in essential acids will be assessed using fasting blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-subject Change in Bone Mineral Density</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Bone mineral density will be assessed with dual-energy x-ray absorptiometry (DEXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-subject Change in Percent Fat Body Mass</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Percent fat body mass will be assessed with DEXA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-subject Change in Percent Lean Body Mass</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Percent lean body mass will be assessed with DEXA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-subject Change in Resting Energy Expenditure</measure>
    <time_frame>Baseline through 12 Months Post-Response (up to 14 months after baseline)</time_frame>
    <description>Resting energy expenditure (kilocalories/day) from Palynziq initiation through 12 months post-response will be assessed using indirect calorimetry and self-reported activity level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in Plasma Neurotransmitters</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>Intra-subject change in neurotransmitter analysis will be assessed using fasting blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in Neuro-QOL - Cognitive Function - Short Form Score</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>The Neuro-QOL Cognitive Function Short Form includes 8 items asking participants about their cognition during the past 7 days. Responses to statements of if cognition problems are occurring are given on a scale from 1 to 5 where 1 = very often and 5 = never. The amount of difficulty experienced from daily life tasks are responded to on a scale from 1 to 5 as 1 = cannot do task and 5 = no difficulty. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more cognition problems than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in Neuro-QOL Sleep Disturbance - Short Form Score</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>The Neuro-QOL Sleep Disturbance Short Form includes 8 items asking participants about their sleep during the past 7 days. Responses to statements of if sleep problems are occurring are given on a scale from 1 to 5 where 1 = never and 5 = always. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more sleep problems than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>The PROMIS Global Health instrument includes 10 items asking participants about their health and quality of life. Responses to items are given on a scale from 1 to 5 where 1 = poor and 5 = excellent. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing greater quality of life than the average person.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in PROMIS-29 Anxiety and Depression Score</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>The PROMIS-29 instrument includes 8 items asking participants about anxiety and depression. Responses to are given on a scale from 1 to 5 where 1 = never and 5 = always. The total summed score from these items ranges from 8 to 40 and higher scores indicate greater anxiety and depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-Study: Change in PROMIS Emotional Support Score</measure>
    <time_frame>12 Months Post-Response through additional four years (5 years post response)</time_frame>
    <description>The PROMIS Emotional Support instrument includes 16 items asking participants about forms of emotional support they have available. Responses to items are given on a scale from 1 to 5 where 1 = never and 5 = always. Raw scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent has greater emotional support than the average person.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Phenylketonurias</condition>
  <arm_group>
    <arm_group_label>Palynziq Therapy for PKU</arm_group_label>
    <description>Participants with PKU who are starting Palynziq therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palynziq</intervention_name>
    <description>Participants will take Palynziq as prescribed by their genetics doctor. In accordance with the Palynziq Risk Evaluation and Mitigation Strategy (REMS) protocol, patients will have their first injection of Palynziq at the Emory Genetics Clinic under the supervision of a physician. After initiating therapy, patients will continue to mail in blood spot filter papers and 3-day dietary records to their clinic providers as standard components of clinical care.</description>
    <arm_group_label>Palynziq Therapy for PKU</arm_group_label>
    <other_name>Pegvaliase</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be obtained to measure amino acids, vitamins, fats, and neurotransmitters.&#xD;
      Blood spots will be obtained to determine the PAH gene mutation of participants.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who have been diagnosed with PKU&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  16 years of age or older&#xD;
&#xD;
          -  diagnosed with PKU through newborn screening or via diagnosis later in life&#xD;
&#xD;
          -  capable of providing consent for medical tests and procedures&#xD;
&#xD;
          -  prescription for Palynziq and be enrolled in the Palynziq Risk Evaluation and&#xD;
             Mitigation Strategy (REMS) program&#xD;
&#xD;
          -  Substudy: Participants must have completed 2&amp;3 of the main study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals who are pregnant&#xD;
&#xD;
          -  unable to provide consent&#xD;
&#xD;
          -  a diagnosis of, or take medication for psychiatric, behavioral, or other inherited&#xD;
             metabolic disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rani Singh, PhD, RDN, LD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rani Singh, PhD, RDN, LD</last_name>
    <phone>778-404-8519</phone>
    <email>rsingh@emory.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Emory University Hospital Georgia Clinical Research Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Rani Singh</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </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/NCT04404530
org study id: IRB00111450
nct id: NCT04404530
lead sponsor: 
collaborator: 
has dmc: Yes
Phenylketonuria (PKU) is an inherited metabolic disorder that impairs the metabolism of the
      essential amino acid phenylalanine (Phe). Without stringent dietary control, Phe accumulates
      in the blood and brain of PKU patients, leading to severe cognitive deficits. Achieving
      metabolic control, defined as blood Phe levels within the range of 120-360 μmol/L, has been a
      significant challenge for PKU patients using traditional diet therapy. The new FDA approved
      pharmacologic treatment, Palynziq, offers a new approach that could significantly reduce the
      burden of PKU by improving blood Phe levels and allowing for a less restrictive diet. As
      little is known about the global metabolic and physiologic effects of Palynziq, the present
      study aims to capture changes in diet quality, neurological health, nutritional status, the
      nutritional metabolome, and patient perceptions of mental and social health with sustained
      Palynziq therapy.
Phenylketonuria (PKU) is an autosomal recessive disorder caused by more than 500 pathogenic
      variants in the phenylalanine hydroxylase (PAH) gene. Due to these mutations, affected
      individuals have reduced activity or complete deficiency of the enzyme phenylalanine
      hydroxylase, which metabolizes the essential amino acid phenylalanine (Phe) to tyrosine.
      Consequently, Phe and its byproducts accumulate in the blood and brain of PKU patients, which
      can have irreparable physical and neurocognitive effects. These may include intellectual
      disabilities, seizures, eczema, psychosis, and hypopigmentation. To prevent these adverse
      conditions, early diagnosis and meticulous control of blood Phe levels are required. For
      optimal metabolic control, the American College of Medical Genetics (ACMG) recommends
      lifelong maintenance of Phe concentrations within the range of 120-360 μmol/L.

      Diet therapy has dramatically improved metabolic control and nutritional status in PKU
      patients and when adherent to dietary treatment, numerous patients have been able to achieve
      normal growth and prevent severe cognitive deficits. This, however, is not an easy task given
      a steep restriction of intact protein is required to keep blood Phe levels within the
      therapeutic range. To meet nutritional needs in the absence of dietary protein, patients
      consume large volumes of Phe-free amino acid formulas (medical food) and specialized
      low-protein modified foods. While this regimen may improve overall diet quality, due to the
      fortification of formula with vitamins and minerals, the poor palatability and high cost
      medical food makes diet therapy a significant burden for patients and their families.

      Pharmacologic therapies now provide an innovative approach to improve patient health and
      quality of life by liberalizing the traditional protein-restricted diet. Palynziq is a
      PEGylated recombinant of phenylalanine lyase, which can lower blood Phe concentrations. Given
      increasing numbers of PKU patients will be initiating Palynziq therapy, it is essential to
      prospectively evaluate the impact of this novel treatment on the neurological health, diet
      quality, and nutritional metabolome of patients when administered in a clinical setting. This
      knowledge will not only improve the efficacy of the treatment, but will be essential for
      expanding the current dietary guidelines to meet the unique needs of patients treated with
      Palynziq.

      The objectives of this proposal are to obtain information on the diet quality, neurological
      health, and nutritional metabolome of patients with PKU at baseline and after intervention
      with Palynziq. This is a three-year observational study that includes non-pregnant adults who
      have PKU and have obtained a physician's prescription to initiate Palynziq treatment.
      Patients who complete three year study are now eligible to participate in a sub study which
      extends the main protocol for up to four years.
observational model: Case-Only
time perspective: Prospective
measure: Intra-subject Change in Intact Protein Intake
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Intra-subject change in intact protein intake will be assessed by participant-reported 3-day dietary records.
measure: Intra-subject Change in Medical Food Protein Intake
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.
measure: Sub study: Intra-subject change in intact protein and medical food protein intake.
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.
measure: Change in Average Intact Protein Intake
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: Average intact protein intake will be determined by participant-reported 3-day dietary records.
measure: Days From Palynziq Initiation to Response
time frame: Baseline up to Response (up to 60 days)
description: The average length of time (in days) from Palynziq initiation until response, as defined by three consecutive plasma Phe levels lower than the upper limit of the recommended treatment range (<360 μmol/L) and a significant increase in intact protein intake (at least 60 percent of the dietary reference intake (DRI) or a two-fold increase from baseline diet prescription), will be determined.
measure: Days From Palynziq Initiation to Consumption of Dietary Reference Intake for Intact Protein
time frame: Baseline up to 12 Months Post-Response (up to 14 months after baseline)
description: The average length of time (in days) from Palynziq initiation it takes for participants to consume the dietary reference intake for intact protein (46g females, 56g males).
measure: Change in Neuro-QOL - Cognitive Function - Short Form Score
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: The Neuro-QOL Cognitive Function Short Form includes 8 items asking participants about their cognition during the past 7 days. Responses to statements of if cognition problems are occurring are given on a scale from 1 to 5 where 1 = very often and 5 = never. The amount of difficulty experienced from daily life tasks are responded to on a scale from 1 to 5 as 1 = cannot do task and 5 = no difficulty. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more cognition problems than the average person.
measure: Change in Neuro-QOL Sleep Disturbance - Short Form Score
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: The Neuro-QOL Sleep Disturbance Short Form includes 8 items asking participants about their sleep during the past 7 days. Responses to statements of if sleep problems are occurring are given on a scale from 1 to 5 where 1 = never and 5 = always. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more sleep problems than the average person.
measure: Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: The PROMIS Global Health instrument includes 10 items asking participants about their health and quality of life. Responses to items are given on a scale from 1 to 5 where 1 = poor and 5 = excellent. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing greater quality of life than the average person.
measure: Change in PROMIS-29 Anxiety and Depression Score
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: The PROMIS-29 instrument includes 8 items asking participants about anxiety and depression. Responses to are given on a scale from 1 to 5 where 1 = never and 5 = always. The total summed score from these items ranges from 8 to 40 and higher scores indicate greater anxiety and depression.
measure: Change in PROMIS Emotional Support Score
time frame: Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline)
description: The PROMIS Emotional Support instrument includes 16 items asking participants about forms of emotional support they have available. Responses to items are given on a scale from 1 to 5 where 1 = never and 5 = always. Raw scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent has greater emotional support than the average person.
measure: Change in Plasma Neurotransmitters
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Intra-subject change in neurotransmitter analysis will be assessed using fasting blood samples.
measure: Change in Plasma Amino Acids
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Intra-subject change in plasma amino acids will be assessed using fasting blood samples.
measure: Change in Essential Fatty Acids
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Intra-subject change in essential acids will be assessed using fasting blood samples.
measure: Intra-subject Change in Bone Mineral Density
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Bone mineral density will be assessed with dual-energy x-ray absorptiometry (DEXA)
measure: Intra-subject Change in Percent Fat Body Mass
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Percent fat body mass will be assessed with DEXA.
measure: Intra-subject Change in Percent Lean Body Mass
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Percent lean body mass will be assessed with DEXA.
measure: Intra-subject Change in Resting Energy Expenditure
time frame: Baseline through 12 Months Post-Response (up to 14 months after baseline)
description: Resting energy expenditure (kilocalories/day) from Palynziq initiation through 12 months post-response will be assessed using indirect calorimetry and self-reported activity level.
measure: Sub-Study: Change in Plasma Neurotransmitters
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: Intra-subject change in neurotransmitter analysis will be assessed using fasting blood samples.
measure: Sub-Study: Change in Neuro-QOL - Cognitive Function - Short Form Score
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: The Neuro-QOL Cognitive Function Short Form includes 8 items asking participants about their cognition during the past 7 days. Responses to statements of if cognition problems are occurring are given on a scale from 1 to 5 where 1 = very often and 5 = never. The amount of difficulty experienced from daily life tasks are responded to on a scale from 1 to 5 as 1 = cannot do task and 5 = no difficulty. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more cognition problems than the average person.
measure: Sub-Study: Change in Neuro-QOL Sleep Disturbance - Short Form Score
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: The Neuro-QOL Sleep Disturbance Short Form includes 8 items asking participants about their sleep during the past 7 days. Responses to statements of if sleep problems are occurring are given on a scale from 1 to 5 where 1 = never and 5 = always. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing more sleep problems than the average person.
measure: Sub-Study: Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: The PROMIS Global Health instrument includes 10 items asking participants about their health and quality of life. Responses to items are given on a scale from 1 to 5 where 1 = poor and 5 = excellent. Scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent in experiencing greater quality of life than the average person.
measure: Sub-Study: Change in PROMIS-29 Anxiety and Depression Score
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: The PROMIS-29 instrument includes 8 items asking participants about anxiety and depression. Responses to are given on a scale from 1 to 5 where 1 = never and 5 = always. The total summed score from these items ranges from 8 to 40 and higher scores indicate greater anxiety and depression.
measure: Sub-Study: Change in PROMIS Emotional Support Score
time frame: 12 Months Post-Response through additional four years (5 years post response)
description: The PROMIS Emotional Support instrument includes 16 items asking participants about forms of emotional support they have available. Responses to items are given on a scale from 1 to 5 where 1 = never and 5 = always. Raw scores are scaled to a T-score with a mean of 50 and a standard deviation of 10. Scores higher than 50 indicate that the respondent has greater emotional support than the average person.
arm group label: Palynziq Therapy for PKU
description: Participants with PKU who are starting Palynziq therapy.
intervention type: Drug
intervention name: Palynziq
description: Participants will take Palynziq as prescribed by their genetics doctor. In accordance with the Palynziq Risk Evaluation and Mitigation Strategy (REMS) protocol, patients will have their first injection of Palynziq at the Emory Genetics Clinic under the supervision of a physician. After initiating therapy, patients will continue to mail in blood spot filter papers and 3-day dietary records to their clinic providers as standard components of clinical care.
arm group label: Palynziq Therapy for PKU
other name: Pegvaliase
Blood samples will be obtained to measure amino acids, vitamins, fats, and neurotransmitters.
      Blood spots will be obtained to determine the PAH gene mutation of participants.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Rani Singh, PhD, RDN, LD
role: Principal Investigator
affiliation: Emory University
last name: Rani Singh, PhD, RDN, LD
phone: 778-404-8519
email: rsingh@emory.edu
facility: 
status: Recruiting
facility: 
status: Recruiting
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Rani Singh
investigator title: Professor
mesh term: Phenylketonurias
sharing ipd: No