The Impact of Phenylalanine Elevations on Metabolic, Cognitive, and Neural Functioning in Adults Heterozygous for Phenylketonuria (PKU)
Sponsor study identifier
Secondary identifiers
interventional
36
1 country
1
Study Start
December 19, 2025
Actual (reported)Primary Completion
March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Study Completion
March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
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:
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
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Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
October 20, 2025
Actual (reported)October 23, 2025
Actual (reported)December 19, 2025
Actual (reported)March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Blood Phenylalanine Levels
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Brain Phenylalanine Levels
Brain Phenylalanine Levels estimated using magnetic resonance spectroscopy (MRS)
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Brain Phenylalanine-to-Tyrosine Ratio
Ratio of Phenylalanine-to-Tyrosine concentrations in the brain as estimated using magnetic resonance spectroscopy (MRS)
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
Pattern of brain activation as captured using functional MRI while performing a go/no-go inhibitory task
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Operational Span Task
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.
Brain concentrations of glutamate, glutathione, creatine, and other metabolites
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
PROMIS Anxiety - Short Form 8a
Baseline only
PROMIS Depression - Short Form 8a
Baseline only
PROMIS Sleep - Short Form 8a
Baseline only
PROMIS Fatigue - Short Form 8a
Baseline only
Heterozygous carriers of a pathogenic variant of the PAH gene associated with phenylketonuria (PKU)
Individuals who do not carry a pathogenic variant of the PAH gene
Oral ingestion of phenylalanine (Phe)
Oral ingestion of Placebo (Vitamin C)
University of Missouri-Columbia
Columbia, Missouri, 65201, United States
First Submitted
October 20, 2025
First Posted
October 23, 2025
Study Start
December 19, 2025
Actual (reported)Primary Completion
March 1, 2027
Estimated3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Multi-Source Interference Task
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.
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Grooved Pegboard Test
Performance-based measure of processing speed \& fine motor control
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Resting-State Functional Connectivity
Synchronization of neural activity within brain networks as measured by functional MRI while participants are at rest
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
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Planned date reported by the registry; this milestone is not confirmed as achieved.
Study Completion
March 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Last Updated
October 22, 2026
Record last verified: 2026-10
Demographic, blood amino acid levels, cognitive test performance, and MRI data (structural, spectroscopy, functional) will be acquired from 18 healthy adult carriers for PKU and 18 matched healthy controls. All data will be de-identified prior to deposit in the NIMH Data Archive (NDA).
Download the complete ClinicalTrials.gov record imported by Syfrah, including fields not shown in this page. The registry may contain a newer revision.
Source: ClinicalTrials.gov.
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