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

NCT ID: NCT05356377

Last Updated: 2025-12-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-25
• Study Completion Date: 2025-07-01

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.

Detailed Description

Past studies have documented PKU-related disruptions in brain phenylalanine (Phe) levels, white matter (WM) and gray matter (GM) brain structures, functional connectivity, and neurocognitive functioning. Additional research suggests that the disruptive effects of excessive blood Phe levels likely contribute to these abnormalities, and treatment aimed at lower Phe levels may lead to significant improvements.

Within this context, the primary aim is to test the hypotheses that Palynziq-related reductions in blood Phe levels will be associated with:

1. A decrease in brain Phe levels as measured by magnetic resonance spectroscopy (MRS).

2. A decrease in the extent and severity of WM abnormalities as evidenced by increased mean diffusivity values - a measure of microstructural WM integrity that is derived via diffusion-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

3. Closer-to-normal volumetric measurements for GM structures. Nature of this effect will be dependent on structure. For example, PKU is associated with increased volume in basal ganglia but decreased volume in posterior cortex and cerebellum (Aldridge et al., 2020; Bodner et al., 2012; Christ et al., 2016).

4. An increase in functional connectivity within the brain's functional networks as measured by resting state functional MRI (fMRI).

5. Improved performance on neurocognitive tests of executive function, attention, processing speed, and motor control.

To accomplish this aim, a total sample of up to 13 adults with PKU who have previously completed baseline (pre-Palnyziq) neurocognitive and neuroimaging evaluations will be recruited from the two sites (University of Missouri, Boston Children's Hospital). Participants will be reassessed following a significant and prolonged Phe response to Palynziq (as reflected by at least 3 consecutive months of Phe levels below 360 μmol/L).

Conditions

Phenylketonurias

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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).

Pegvaliase-Pqpz

Intervention Type: DRUG

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

Interventions

Pegvaliase-Pqpz

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

University of Missouri-Columbia

OTHER

Sponsor Role: lead

Responsible Party

Shawn Christ

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shawn Christ, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

University of Missouri

Columbia, Missouri, United States

Countries

United States

Other Identifiers

2055562

Identifier Type: -

Identifier Source: org_study_id