Autosomal Recessive Disorder (Genetic Carriers of PKU)
Conditions
Brief summary
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 mixed into 250 mL water with 1 tsp white sugar. 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.
Interventions
DIETARY_SUPPLEMENTL-Phenylalanine
100 mg/kg
Sponsors
McMaster University
University of Guelph
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
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stop Signal Reaction Time (Response Inhibition) | Change from baseline to 2-hours post L-Phe supplementation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phenylalanine 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 | Change from baseline to 2-hours post L-Phe supplementation | Profile of Mood States (POMS) Outcome |
| Blood Pressure | Change from baseline to 1-hour and 2-hours post L-Phe supplementation | Systolic and Diastolic |
| Working Memory | Change from baseline to 2-hours post L-Phe supplementation | N-Back Test Outcome |
| Stop Signal Delay | Change from baseline to 2-hours post L-Phe supplementation | Stop Signal Task Outcome |
| Individual Coefficient of Variance (Variability in Reaction Times) | Change from baseline to 2-hours post L-Phe supplementation | Stop Signal Task Outcome |
| Tyrosine Levels | Change from baseline to 2-hours post L-Phe supplementation | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Impulsivity | Baseline | BIS-Brief Outcome |
| 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 |
| Chronic Depression | Baseline | PHQ-9 Outcome |
| Chronic Anxiety | Baseline | GAD-7 Outcome |
Countries
Canada
Outcome results
None listed