Preliminary Study of Brain Effects of Palynziq-Related Changes in Phenylalanine in Individuals With PKU

NCT05356377 | Completed

• 1 other identifier: 2055562
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of the proposed study is to elucidate neurologic and neuropsychological improvements associated with Palynziq-related reduction in plasma Phe levels in individuals with PKU. To this end, investigators will utilize state-of-the-art neuropsychological and multi-modal neuroimaging methods to examine the effects of large Phe level reduction (levels \<360 μmol/L for at least 3 consecutive months) on GM and WM brain structures, brain concentrations of Phe, functionality of brain networks, and associated cognitive functioning in a sample of individuals with PKU who are being treated with Palyzniq.

Conditions

Phenylketonurias

Outcome Measures

Primary Outcomes (2)

• Neurologic Integrity

  Brain phenylalanine (Phe) levels, white matter integrity, gray matter integrity, functional connectivity as measured using magnetic resonance imaging (MRI)

  Single timepoint for 1 hour

• Neuropsychological Functioning

  Neuropsychological functioning as assessed using a comprehensive battery of standardized neuropsychological tests

  Single timepoint for 2 hours

Secondary Outcomes (2)

• Cookie Theft Picture Test

  Single timepoint for 10 minutes

• In-the-moment Psychoemotional Symptomatology

  30 minutes total per day for 7 consecutive days

Study Arms (1)

PKU Palynziq Group

Individuals with PKU who have previously completed baseline (pre-Palnyziq) neurocognitive and neuroimaging evaluations and have since demonstrated a significant and prolonged Phe response to Palynziq (as reflected by at least 3 consecutive months of Phe levels below 360 μmol/L).

Drug: Pegvaliase-Pqpz

Interventions

Pegvaliase-Pqpz DRUG

Participants will have been prescribed pegvaliase-pqpz (Palynziq) by their primary metabolic care providers as part of their standard care. \[Note that prescription and standard care are independent of the present study.\]

PKU Palynziq Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants who meet 3 primary criteria: (1) have previously completed baseline (pre-Palynziq) neurocognitive \& neuroimaging evaluations as part of other studies at University of Missouri of Boston Children's Hospital, (2) have since been prescribed Palnyziq by their primary metabolic care providers, and (3) have demonstrated a prolonged blood phe response to Palynziq as reflected by 3+ months of phe levels below 360 umol/L.

You may qualify if:

• Age 18-55 years
• Participants identified by newborn screening with PKU as evidenced by a blood Phe level ≥ 360μmol/L; received treatment within the first 30 days of life
• Previously received a neuropsychological and neuroimaging evaluation (as part of previously described MU or BCH studies) prior to enrollment in the present study (while Palynziq-naïve).
• Capable of providing informed consent
• Presently being treated with Palynziq and has demonstrated a prolonged Phe response to Palynziq (as reflected by at least 3 consecutive months of Phe levels below 360 μmol/L)

You may not qualify if:

• History of major neurologic disorder unrelated to PKU
• Contraindications for safe MRI participation such as (a) pregnancy or plans to become pregnant during period of study enrollment; or (b) metallic objects inside the body (e.g., surgical staples left in the body following surgery, middle ear prosthesis, metal foreign objects lodged inside the eye, heart pacemakers).
• Current participation in an interventional clinical trial (not Palynziq-related).

Sponsors & Collaborators

• BioMarin Pharmaceutical: collaborator
• University of Missouri-Columbia: lead

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Missouri

Columbia, Missouri, 65211, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

pegvaliase

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Shawn Christ, PhD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 2, 2022
• Study Start: May 25, 2022
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: December 29, 2025

Record last verified: 2025-12

Locations

US (2)