NCT07220265 · University of Missouri-Columbia
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
What this study is about
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).
View original scientific description
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.
Interventions
DIETARY_SUPPLEMENT
Phenylalanine (Phe)
Oral ingestion of phenylalanine (Phe)
DIETARY_SUPPLEMENT
Placebo
Oral ingestion of Placebo (Vitamin C)
Primary outcome measures
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 Levels estimated using magnetic resonance spectroscopy (MRS)
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
Ratio of Phenylalanine-to-Tyrosine concentrations in the brain as estimated using magnetic resonance spectroscopy (MRS)
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
Pattern of brain activation as captured using functional MRI while performing a go/no-go inhibitory task
Operational Span Task
Time frame: 3 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 Task
Time frame: 3 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 Test
Time frame: 3 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 Connectivity
Time frame: 3 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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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).
Where
- Columbia, Missouri
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 11, 2026 · Source of record for eligibility and locations