PKU Carriers Trial (Pilot Study): Impact on Cognition, Mental Health, Blood Pressure and Metabolism

Study Overview
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Brief Summary
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This is a clinical intervention pilot/feasibility 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-Brief). 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). 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 will also be measured at baseline. Following baseline tests, participants will consume a pure L-Phe supplement dosed at 100 mg/kg. Blood pressure 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 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.

Official Title
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A Pilot Study for the PKU Carriers Trial: Evaluating the Impact of PKU Carrier Status on Cognition, Mental Health, Blood Pressure and L-phenylalanine Metabolism

Conditions
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Autosomal Recessive Disorder (Genetic Carriers of PKU)

Intervention / Treatment
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* Dietary Supplement: L-Phenylalanine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Known 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 Taking a Monoamine Oxidase Inhibitor anti-depressant Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genetic Carriers and Non-Carriers of PKU<br> | Dietary Supplement: L-Phenylalanine<br>* 100 mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stop Signal Reaction Time (Response Inhibition) |  | Change from baseline to 2-hours post L-Phe supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working Memory | N-Back Test Outcome | Change from baseline to 2-hours post L-Phe supplementation | 
| Stop Signal Delay | Stop Signal Task Outcome | Change from baseline to 2-hours post L-Phe supplementation | 
| Individual Coefficient of Variance (Variability in Reaction Times) | Stop Signal Task Outcome | Change from baseline to 2-hours post L-Phe supplementation | 
| Phenylalanine Levels |  | Change from baseline to 2-hours post L-Phe supplementation | 
| Tyrosine Levels |  | Change from baseline to 2-hours post L-Phe supplementation | 
| Phenylalanine Metabolites: e.g.phenylethylamine, tyramine, phenylpyruvate, others |  | Change from baseline to 2-hours post L-Phe supplementation | 
| Tyrosine Metabolites: e.g. L-DOPA, dopamine, norepinephrine, epinephrine, p-hydroxyphenylpyruvate, homogentisic acid, fumarate, others |  | Change from baseline to 2-hours post L-Phe supplementation | 
| Mood | Profile of Mood States (POMS) Outcome | Change from baseline to 2-hours post L-Phe supplementation | 
| Blood Pressure | Systolic and Diastolic | Change from baseline to 1-hour and 2-hours post L-Phe supplementation |