Understanding Phenylalanine's Impact on Brain and Cognition in PKU Carriers

This study aims to understand how elevated phenylalanine (Phe) levels affect the brain and thinking abilities in adults who are carriers of Phenylketonuria (PKU). Researchers will compare PKU carriers with healthy individuals who are not carriers. You would receive either phenylalanine (a dietary supplement) or a placebo (Vitamin C). The study will look at your blood and brain phenylalanine levels, and how your brain activity and thinking skills change after taking the supplement or placebo. This will help us learn if PKU carriers experience prolonged high brain Phe levels or changes in thinking after consuming Phe. The study plans to enroll 36 participants, but its current status is unclear.

Study design
This is an interventional study involving 36 participants, including both PKU carriers and non-carriers. It is a double-blind crossover study, meaning neither you nor the researchers will know if you are receiving phenylalanine or placebo at a given time.
What's involved
You would have blood and brain phenylalanine levels measured at three timepoints: before taking the supplement/placebo, and then 2 and 4 hours after. You would also perform cognitive tests and brain scans (fMRI) at these same timepoints.
Compensation
Not stated in the trial record.
Follow-up
Your blood and brain levels, and cognitive function, will be assessed up to 4 hours after taking the phenylalanine or placebo.

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NCT07220265

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

Recruiting
NAAges 18–60InterventionalBasic science
University of Missouri-Columbia
~36 participants
Updated 2026-03-11 on ClinicalTrials.gov
What's tested:Phenylalanine (Phe)Placebo

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Blood Phenylalanine Levels
Measured over 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
+7 more outcomes measured
Carrier of Phenylketonuria
Healthy
1 sites across 1 states
Missouri1

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Eligibility criteria

Inclusion

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

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).
  • Blood Phenylalanine Levels3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
  • Brain Phenylalanine Levels3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Brain Phenylalanine Levels estimated using magnetic resonance spectroscopy (MRS)

  • Brain Phenylalanine-to-Tyrosine Ratio3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Ratio of Phenylalanine-to-Tyrosine concentrations in the brain as estimated using magnetic resonance spectroscopy (MRS)

  • Neural Activity during Go/No-Go Task3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Pattern of brain activation as captured using functional MRI while performing a go/no-go inhibitory task

  • Operational Span Task3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Performance-based measure of working memory ability. In this task, participants first solve a math problem and then see a letter, and then solve another math problem, and see another letter. This math-letter sequence is repeated from three to seven times for each trial with an unpredictable length each time. After each math-letter sequence, participants are asked to recall, in order, the preceding letters. Scores are calculated by summing the number of letters correctly recalled in the correct order.

  • Multi-Source Interference Task3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Performance-based measure of focused attention. ). In this task, participants are shown a display containing three horizontally-aligned numbers (i.e., 1, 2, or 3) and asked to respond as quickly as possible to the location (position #1, 2, or 3) of the number stimulus that is different from the others. The location may be congruent (e.g., "323") or incongruent (e.g., "112") with identity of the target number. Mean response time and error rate will served as the outcome variables.

  • Grooved Pegboard Test3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Performance-based measure of processing speed \& fine motor control

  • Resting-State Functional Connectivity3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

    Synchronization of neural activity within brain networks as measured by functional MRI while participants are at rest