RecruitingNot Applicable

Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers

United States36 participantsStarted 2025-12-19

Plain-language summary

The goal of this clinical trial is to advance our understanding of the cognitive and neurophysiologic sequelae associated with suboptimal phenylalanine (Phe) metabolism in heterozygous carriers of phenylketonuria (PKU). The main questions it aims to answer are: * Do PKU carriers experience prolonged elevations in brain Phe levels following oral ingestion of dietary Phe? * Do PKU carriers experience disruptions in cognitive functioning following oral ingestion of dietary Phe? * Do PKU carriers experience atypical brain activity following oral ingestion of dietary Phe? Researchers will compare PKU carriers and non-carriers following oral ingestion of dietary Phe and a placebo. Participants will: * Consume Phe or a placebo at two separate visits to our facility * At each visit, they will complete a series of MRIs and cognitive tests throughout the day

Who can participate

Age range18 Years – 60 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Age 18-60 years * For the PKU carrier group: Individuals who are the parent of an individual with PKU or who are otherwise have confirmed PKU carrier status (e.g., a sibling of someone with PKU who has had genetic testing done) * For the non-carrier group: Individuals who do not have PKU or a family history of PKU Exclusion Criteria: * Obesity as defined by a body mass index (BMI) over 30\* * Taking oral contraceptives on the day of testing session\* * Positive cotinine urine test showing nicotine use * History of major neurologic condition (e.g., multiple sclerosis, severe closed head injury, Parkinson's disease)) unrelated to PKU and known to adversely impact brain health and function * 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).

What they're measuring

Blood Phenylalanine Levels

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Brain Phenylalanine Levels

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Brain Phenylalanine-to-Tyrosine Ratio

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Neural Activity during Go/No-Go Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Operational Span Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Multi-Source Interference Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Grooved Pegboard Test

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Trial details

NCT IDNCT07220265

SponsorUniversity of Missouri-Columbia

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-12-31

Contact for this trial

Shawn Christ

573-884-8140 christse@missouri.edu

View on ClinicalTrials.gov More Carrier of Phenylketonuria trials

Plain-language summary

Who can participate

Age range18 Years – 60 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Blood Phenylalanine Levels

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Brain Phenylalanine Levels

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Brain Phenylalanine-to-Tyrosine Ratio

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Neural Activity during Go/No-Go Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Operational Span Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Multi-Source Interference Task

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Grooved Pegboard Test

Timeframe: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo