PhenylketonuriasNCT05356377
Preliminary Study of Brain Effects of Palynziq-Related Changes in Phenylalanine in Individuals With PKU
An observational study of Phenylketonurias, run by University of Missouri-Columbia at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Phenylketonurias
- What is being tested?
- Pegvaliase-Pqpz
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 May 2022to 1 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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)
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Missouri
Columbia, Missouri, 65211
About this study
Official title: A Preliminary Study of the Neurological and Neuropsychological Effects of Palynziq-Related Changes in Phenylalanine in Individuals With Phenylketonuria (PKU)
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.
Read the 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:
- A decrease in brain Phe levels as measured by magnetic resonance spectroscopy (MRS).
- 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).
- 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).
- An increase in functional connectivity within the brain's functional networks as measured by resting state functional MRI (fMRI).
- 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
- Being tested
- Pegvaliase-Pqpz
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegvaliase-PqpzDrug
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.]
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Pegvaliase-Pqpz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurologic Integrity
Brain phenylalanine (Phe) levels, white matter integrity, gray matter integrity, functional connectivity as measured using magnetic resonance imaging (MRI)
Measured: Single timepoint for 1 hour
Neuropsychological Functioning
Neuropsychological functioning as assessed using a comprehensive battery of standardized neuropsychological tests
Measured: Single timepoint for 2 hours
Secondary outcomes (2)
Cookie Theft Picture Test
Verbal linguistics as assessed using the Cookie Theft Picture Test from the Boston Diagnostic Aphasia Exam
Measured: Single timepoint for 10 minutes
In-the-moment Psychoemotional Symptomatology
Cell phone-based ecological momentary assessment (EMA) to measure in-the-moment psychoemotional symptomatology
Measured: 30 minutes total per day for 7 consecutive days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2022
- Study start25 May 2022
- Primary completion1 Jul 2025
- Study completion1 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriasStudies of the same condition, open and under way.
- More trials run by University of Missouri-ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Principal investigator, Shawn Christ, University of Missouri-Columbia
- Investigators
- Shawn Christ, PhD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05356377
- Sponsor's protocol ID
- 2055562
- Status last verified
- Dec 2025
- First submitted
- 27 Apr 2022
- Last updated
- 29 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Preliminary Study of the Neurological and Neuropsychological Effects of Palynziq-Related Changes in Phenylalanine in Individuals With Phenylketonuria (PKU)
- ClinicalTrials.gov ID
- NCT05356377
- Acronym / sponsor ID
- 2055562
- Conditions
- Phenylketonurias
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- 25 May 2022 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 2 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- A decrease in brain Phe levels as measured by magnetic resonance spectroscopy (MRS).
- 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).
- 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).
- An increase in functional connectivity within the brain's functional networks as measured by resting state functional MRI (fMRI).
- 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).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PKU Palynziq Group | – | Drug: Pegvaliase-PqpzIndividuals 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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pegvaliase-PqpzParticipants 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.] | Drug | PKU Palynziq Group |
Primary outcome
Neurologic Integrity
Time frame: Single timepoint for 1 hour
Brain phenylalanine (Phe) levels, white matter integrity, gray matter integrity, functional connectivity as measured using magnetic resonance imaging (MRI)
Neuropsychological Functioning
Time frame: Single timepoint for 2 hours
Neuropsychological functioning as assessed using a comprehensive battery of standardized neuropsychological tests
2 secondary outcomes
Cookie Theft Picture Test
Time frame: Single timepoint for 10 minutes
In-the-moment Psychoemotional Symptomatology
Time frame: 30 minutes total per day for 7 consecutive days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shawn Christ, PhD principal investigator
University of Missouri-Columbia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Phenylketonurias, run by University of Missouri-Columbia at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurologic Integrity (time frame: Single timepoint for 1 hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2025; AzTrials last refreshed its copy on 7 Nov 2026.