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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Autosomal Recessive Disorder (Genetic Carriers of PKU)
• Intervention / Treatment: Dietary supplement: L-Phenylalanine

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Justine R Keathley, PhD; Phone Number: (519) 824-4120; Email: jkeathle@uoguelph.ca

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 2W1
      • Recruiting
      • University of Guelph
      • Contact: Justine R Keathley, PhD; Email: jkeathle@uoguelph.ca
      • Sub-Investigator: Mazyar Fallah, PhD
      • Sub-Investigator: Philip Millar, PhD
      • Sub-Investigator: Sophia Khan, BSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetic Carriers and Non-Carriers of PKU	Dietary supplement: L-Phenylalanine; 100 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic Anxiety	GAD-7 Outcome	Baseline
Chronic Depression	PHQ-9 Outcome	Baseline
Impulsivity	BIS-Brief Outcome	Baseline
Trial-by-trial analysis	To be conducted if there are significant findings from the four main stop signal task outcomes	Change from baseline to 2-hours post L-Phe supplementation

Collaborators and Investigators

• Sponsor: University of Guelph
• Collaborators: McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: REB23-03-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No