Phe for Me? The Effects of L-Phe on PKU Carriers and Non-carriers

NCT06119048 — Not applicable, Completed, 56 participants, University of Guelph

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Phe for Me? A Precision Nutrition Clinical Trial of Metabolic, Cardiovascular, and Neurocognitive Responses to Phenylalanine Among Carriers and Non-carriers of PKU

Registry	NCT06119048, acronym Phe for Me
Status	Completed
Phase	Not applicable
Study type	Interventional; na, single group, masking: none, other
Enrollment	56 (Actual)
Sponsor	University of Guelph (Other); collaborators: McMaster University, Laval University
Conditions	Autosomal Recessive Disorder (Genetic Carriers of PKU)
Interventions	L-Phenylalanine (Dietary supplement)
Dates	start 2024-06-18, primary completion 2025-10-03, completion 2025-10-03, first posted 2023-11-07, last updated 2026-05-04
Locations	1 site in Canada

-Summary

This is a clinical intervention study of PKU carriers (cases) and non-carriers (controls). Upon completing the informed consent process, participants will complete baseline measures of chronic mental health prior to the intervention (PHQ-9, GAD-7, BIS-11). Participants will attend the Human Nutraceutical Research Unit (HNRU) at the University of Guelph, fasted, and first undergo baseline measures of cognition and acute mental health (mood) and provide samples or saliva, urine and dried blood spots to evaluate phenylalanine (Phe), tyrosine (Tyr) and their metabolites (PAH pathway functioning) as well as for genetic testing of the PAH gene. Participants will also complete a brief questionnaire which will include age, sex, ethnicity, income, weight and height (measured using a stadiometer and calibrated weigh scale), and confirmation that participants arrived to the lab fasted (i.e. have only had water to drink and no other foods/ beverages prior to analyses). Blood pressure and heart rate will also be measured at baseline.

Following baseline tests, participants will consume a pure L-Phe supplement dosed at 100 mg/kg mixed with 125 mL of water and 125mL of orange juice. Blood pressure and heart rate will be repeated at 1-hour post-L-Phe consumption. Two-hours postprandial, participants will repeat the cognitive tests and acute mental health (mood) assessment, blood pressure and heart rate measurement and provide follow-up saliva, urine and dried blood spot samples. Participants will also be asked to report any side effects they experienced with the L-Phe consumption.

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+Arms and interventions

Arm	Type	Interventions	Description
Genetic Carriers and Non-Carriers of PKU	Experimental	Dietary Supplement: L-Phenylalanine

L-Phenylalanine (Dietary supplement): 100 mg/kg

+Outcome measures

Primary outcomes

Stop Signal Reaction Time [Change from baseline to 2-hours post L-Phe supplementation]: Response Inhibition

Secondary outcomes

Working Memory [Change from baseline to 2-hours post L-Phe supplementation]: N-Back Test Outcome
Individual Coefficient of Variance (Variability in Reaction Time) [Change from baseline to 2-hours post L-Phe supplementation]: Stop Signal Task Outcome
Phenylalanine Levels [Change from baseline to 2-hours post L-Phe supplementation]: Blood, saliva and urine sample analyses
Tyrosine Levels [Change from baseline to 2-hours post L-Phe supplementation]: Blood, saliva and urine sample analyses
Phenylalanine Metabolites [Change from baseline to 2-hours post L-Phe supplementation]: e.g. phenylethylamine, tyramine, phenylpyruvate, others
Tyrosine Metabolites [Change from baseline to 2-hours post L-Phe supplementation]: e.g. L-DOPA, dopamine, norepinephrine, epinephrine, p-hydroxyphenylpyruvate, homogentisic acid, fumarate, others
Mood [Change from baseline to 2-hours post L-Phe supplementation]: Profile of Mood State (POMS) Outcome
Blood Pressure [Change from baseline to 1-hour and 2-hours post L-Phe supplementation]: Systolic and Diastolic
Heart rate [Change from baseline to 1-hour and 2-hours post L-Phe supplementation]: BPM
Side Effects Following L-Phe Consumption [0-3 hours post L-Phe consumption]: To be monitored throughout the visit to the research unit

Other outcomes

Chronic Anxiety [Baseline]: GAD-7 Outcome (higher scores indicate worse anxiety: range of 0 to >15)
Chronic Depression [Baseline]: PHQ-9 Outcome (higher scores indicate worse depression: range of 0 to 27)
Impulsivity [Baseline]: BIS-11 Outcome (higher scores indicate more impulsivity: range 30 to 120)
Trial-by-Trial Analysis [Change from baseline to 2-hours post L-Phe supplementation]: to be conducted if there are significant findings from the four main stop signal task outcomes

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Carrier or non-carrier of PKU
* At least 18 Years of age
* Comfortable fasting the morning of the study (no food or drink other than water)

Exclusion Criteria:

* Diagnosed with: PKU, severe neurodegenerative conditions affecting cognition (e.g. Alzheimer's, Parkinson's, dementia), melanoma, hypertension, liver disease and/or kidney disease
* Diagnosed with hypertension or hypotension
* Taking a monoamine oxidase inhibitor anti-depressant
* Pregnant or breastfeeding
* Orange/citrus allergy or intolerance
* Body weight 150 kg or greater
* History of fainting during blood sampling

+Locations (1)

Facility	City	Country	Status
University of Guelph	Guelph, Ontario	Canada

+Publications

Results publication: Khan SM, Fennell ML, Fallah M, Jordan H, Kroezen Z, Britz-McKibbin P, Millar PJ, Heister RR, Vohl MC, Keathley JR. Study protocol and pilot study results for a clinical intervention trial of PKU carriers and non-carriers: the Phe for Me trial. Orphanet J Rare Dis. 2026 Jan 19;21(1):18. doi: 10.1186/s13023-025-04131-2. PMID 41555437