Recruiting

PKU vs. Non-Carriers

Sponsor:

University of Missouri-Columbia

Code:

NCT07220265

Conditions

Carrier of Phenylketonuria

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

Interventions

Phenylalanine (Phe)

Placebo

Study Details

Brief 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

Conditions

Carrier of Phenylketonuria

Healthy

Study ID

NCT07220265

Start date

Dec 19, 2025

Status verified date

Mar, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

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).

Study Design

Enrollment

36 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

other: PKU Carriers

Heterozygous carriers of a pathogenic variant of the PAH gene associated with phenylketonuria (PKU)

other: Non-Carriers

Individuals who do not carry a pathogenic variant of the PAH gene

Interventions

Phenylalanine (Phe)

Oral ingestion of phenylalanine (Phe)

Placebo

Oral ingestion of Placebo (Vitamin C)

Primary outcome measure

  • Blood Phenylalanine Levels [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Brain Phenylalanine Levels [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Brain Phenylalanine-to-Tyrosine Ratio [ Time Frame: 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 [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Operational Span Task [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Multi-Source Interference Task [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Grooved Pegboard Test [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]
  • Resting-State Functional Connectivity [ Time Frame: 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo ]

Central Contacts and Locations

Central contacts

Shawn Christ

573-884-8140christse@missouri.edu

Locations

University of Missouri-Columbia

Recruiting

Columbia, Missouri, United States, 65201

Contacts

Shawn Christ

573-884-8140christse@missouri.edu

More Information

Sponsor

University of Missouri-Columbia

Last update posted

Mar 11, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Missouri-Columbia on 2026-03-11.