Effects of short-term phenylalanine increases on brain and thinking in adult PKU carriers

The Impact of Phenylalanine Elevations on Metabolic, Cognitive, and Neural Functioning in Adults Heterozygous for Phenylketonuria (PKU)

This research will test whether taking a dose of phenylalanine raises brain Phe, changes brain activity on MRI, and temporarily affects thinking in adults who carry the PKU gene compared with non-carriers.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: University of Missouri-Columbia (Academic / other)
• Locations: 1 site (Columbia, Missouri)
• Trial ID: NCT07220265 on ClinicalTrials.gov

What this trial studies

This is a double-blind, crossover study enrolling 18 genetically confirmed heterozygous PKU carriers and 18 non-carrier controls who each receive an oral phenylalanine dose and a placebo on separate visits. At each visit participants complete baseline, 2-hour, and 4-hour assessments including blood tests, MRI scans (resting-state and fMRI n-back working memory task), and a battery of cognitive tests. Brain and blood levels of phenylalanine and tyrosine will be measured at each timepoint to compare time courses between carriers and non-carriers. The repeated-measures design and genetic confirmation aim to detect acute neurophysiologic and cognitive effects of dietary Phe with higher rigor than prior work.

Who should consider this trial

Good fit: Adults aged 18–60 who are genetically confirmed PKU carriers (or healthy non-carrier volunteers without a family history of PKU), medically stable, and eligible for MRI are ideal candidates.

Not a fit: People with major neurologic disorders, BMI over 30, positive nicotine tests, pregnancy or MRI contraindications, or inability to complete repeated in-person MRI sessions are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could clarify whether PKU carriers experience short-term brain or cognitive changes after phenylalanine intake and help shape dietary guidance or monitoring for carriers.

How similar studies have performed: Prior smaller or methodologically limited studies have suggested possible subtle cognitive differences in PKU carriers, but robust, genetically confirmed crossover imaging data are limited, making this approach relatively novel and more rigorous.

Eligibility criteria

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 this trial is running

Columbia, Missouri

• University of Missouri-Columbia — Columbia, Missouri, United States (Recruiting)

Study contacts

• Study coordinator: Shawn Christ

Conditions Carrier of Phenylketonuria; Healthy