ClinicalTrials.gov record NCT07220265
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
The Impact of Phenylalanine Elevations on Metabolic, Cognitive, and Neural Functioning in Adults Heterozygous for Phenylketonuria (PKU)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This randomized, double-blind crossover study compares oral phenylalanine with a placebo in adults who carry a PKU gene variant and in non-carriers. On two separate test days participants take Phe or placebo and undergo MRI scans, cognitive tests, and blood and brain measurements at baseline, 2 hours, and 4 hours. The study aims to learn whether short-term Phe intake affects brain Phe levels, brain activity, or cognitive performance.
What it is studying. Whether oral phenylalanine (compared with placebo) causes prolonged elevations in blood and brain phenylalanine, whether it changes brain activity measured by MRI, and whether it affects performance on cognitive tests in heterozygous PKU carriers versus non-carriers.
What the researchers hope to learn. To improve scientific understanding of how elevated phenylalanine affects brain chemistry, brain activity, and cognitive function in adults who carry a PKU-related gene variant. The study will collect blood and brain measurements and cognitive and MRI outcomes to address these questions.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Dietary supplement
- Phenylalanine (Phe)
- Placebo
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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 description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
Limitations inherent in past studies of phenylketonuria (PKU) carriers (e.g., poor genetic characterization of sample resulting in inclusion of homozygous non-PKU relatives, reliance on rudimentary or overly broad behavioral assessment tools) make it difficult to conclude the extent to which neurophysiologic and cognitive processes are affected in these individuals. To address this gap in the literature, we propose to conduct a double-blind crossover study in a sample of genetically-confirmed sample of 18 heterozygous PKU carriers and 18 non-carriers. A principled investigation of the effects of elevated phenylalanine (Phe) on neurocognition will involve participants performing an fMRI n-back WM task, resting state scan, and a battery of select cognitive tests at 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo. Blood and brain levels of Phe and Tyr will also be assessed at each timepoint.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
You will attend two full-day study visits. At each visit you will take an oral dose (phenylalanine or a placebo); you will receive Phe at one visit and placebo at the other in random order, and the study is double‑blind. During each visit you will undergo brain MRI/MRS scans, perform cognitive and attention tasks, complete some questionnaires (baseline), and give blood samples at baseline, about 2 hours and about 4 hours after dosing to measure Phe and Tyr. Before participation you will have screening checks such as BMI assessment, a urine cotinine test for nicotine, and MRI-safety screening including pregnancy checks where applicable.
How the study is structured. Interventional (randomized, double-blind, crossover). Each participant attends two test visits and receives oral phenylalanine on one visit and placebo on the other (order is randomized and blinded). At each visit participants complete MRI scans (including brain spectroscopy and task fMRI), cognitive tasks, and blood draws at baseline, 2 hours, and 4 hours after ingestion.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on phenylketonuria
Important dates
- Study start
- Dec 19, 2025
- Primary completion
- Dec 31, 2026 (estimated)
- Study completion
- Dec 31, 2026 (estimated)
- Target enrollment
- 36 participants (estimated)
- Last updated on registry
- Mar 11, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- University of Missouri-Columbia
- Principal investigator
- Shawn Christ, Professor, Psychological Sciences
University of Missouri-Columbia - Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Shawn Christ 📞 573-884-8140 ✉ christse@missouri.edu
Participating sites (1)
- University of Missouri-ColumbiaRecruiting
Columbia, Missouri, 65201 · United States
- Shawn Christ · 573-884-8140 · christse@missouri.edu
Terms used on this page · explanations by MedicalUpdates.ai
- placebo
- A treatment that looks like the study treatment but contains no active ingredient. Some participants receive it instead of the study treatment, usually without knowing which they got.
- Contraindications
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- double-blind
- Two types of people involved in the study do not know which intervention a participant is receiving. The ClinicalTrials.gov record specifies who is masked, for example participants, care providers, investigators or outcome assessors.
- crossover
- Each participant receives more than one intervention, one after the other, usually with a gap (a washout) in between. Participants act as their own comparison.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials