Autosomal Recessive Disorder (Genetic Carriers of PKU)
Conditions
Brief 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.
Interventions
DIETARY_SUPPLEMENTL-Phenylalanine
100 mg/kg
Sponsors
University of Guelph
McMaster University
Laval University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stop Signal Reaction Time | Change from baseline to 2-hours post L-Phe supplementation | Response Inhibition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Outcome results
None listed