Nutritional Impacts of Palynziq on Patients With Phenylketonuria (PKU)

NCT ID: NCT04404530

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-08
• Study Completion Date: 2028-12-31

Brief Summary

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.

Detailed Description

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 the three year study are now eligible to participate in a sub-study which extends the main protocol for up to five years.

Conditions

Phenylketonurias

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Palynziq Therapy for PKU

Participants with PKU who are starting Palynziq therapy, or have recently started Palynziq therapy but have not achieved response.

Palynziq

Intervention Type: DRUG

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.

Interventions

Palynziq

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.

Intervention Type: DRUG

Other Intervention Names

Pegvaliase

Eligibility Criteria

Inclusion Criteria

• 16 years of age or older
• diagnosed with PKU through newborn screening or via diagnosis later in life
• capable of providing consent for medical tests and procedures
• prescription for Palynziq and be enrolled in the Palynziq Risk Evaluation and Mitigation Strategy (REMS) program
• Substudy: Participants must have completed visit 2 of the main study

Exclusion Criteria

• unable to provide consent
• a diagnosis of, or take medication for psychiatric, behavioral, or other inherited metabolic disorders

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Rani Singh

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rani Singh, PhD, RDN, LD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Georgia Clinical Research Center

Atlanta, Georgia, United States

Site Status: RECRUITING

The Emory Clinic

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rani Singh, PhD, RDN, LD

Role: CONTACT

rsingh@emory.edu

778-404-8519

Other Identifiers

2025P011579

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00111450

Identifier Type: -

Identifier Source: org_study_id