Health TrialsbyHealthPanel

Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers

ConditionsCarrier of PhenylketonuriaHealthy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-60
SponsorUniversity of Missouri-Columbia

About this trial

The goal of this clinical trial is to advance our understanding of the cognitive and neurophysiologic sequelae associated with suboptimal phenylalanine (Phe) metabolism in heterozygous carriers of phenylketonuria (PKU). The main questions it aims to answer are:

* Do PKU carriers experience prolonged elevations in brain Phe levels following oral ingestion of dietary Phe? * Do PKU carriers experience disruptions in cognitive functioning following oral ingestion of dietary Phe? * Do PKU carriers experience atypical brain activity following oral ingestion of dietary Phe? Researchers will compare PKU carriers and non-carriers following oral ingestion of dietary Phe and a placebo.

Participants will:

* Consume Phe or a placebo at two separate visits to our facility * At each visit, they will complete a series of MRIs and cognitive tests throughout the day

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Age 18-60 years

For the PKU carrier group: Individuals who are the parent of an individual with PKU or who are otherwise have confirmed PKU carrier status (e.g., a sibling of someone with PKU who has had genetic testing done)

For the non-carrier group: Individuals who do not have PKU or a family history of PKU

Disqualifiers

Obesity as defined by a body mass index (BMI) over 30*

Taking oral contraceptives on the day of testing session*

Positive cotinine urine test showing nicotine use

History of major neurologic condition (e.g., multiple sclerosis, severe closed head injury, Parkinson's disease)) unrelated to PKU and known to adversely impact brain health and function

Trial design

Design model

Crossover

Treatments tested in this trial

  • Phenylalanine (Phe)

    Dietary supplement

    Oral ingestion of phenylalanine (Phe)

  • Placebo

    Dietary supplement

    Oral ingestion of Placebo (Vitamin C)

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: PKU CarriersOther 2 interventions
Group B: Non-CarriersOther 2 interventions

Trial outcomes

Primary outcomes

1

Blood Phenylalanine Levels

Time frame
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
2

Brain Phenylalanine Levels

Brain Phenylalanine Levels estimated using magnetic resonance spectroscopy (MRS)

Time frame
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
3

Brain Phenylalanine-to-Tyrosine Ratio

Ratio of Phenylalanine-to-Tyrosine concentrations in the brain as estimated using magnetic resonance spectroscopy (MRS)

Time frame
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
4

Neural Activity during Go/No-Go Task

Pattern of brain activation as captured using functional MRI while performing a go/no-go inhibitory task

Time frame
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo

Secondary outcomes

1

Brain concentrations of glutamate, glutathione, creatine, and other metabolites

Concentrations of various brain metabolites as estimated using magnetic resonance spectroscopy (MRS)

Time frame
3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo
2

PROMIS Anxiety - Short Form 8a

A patient-reported outcome (PRO) measure assessing symptoms of anxiety. Scores range from 8 to 40, with higher scores indicating more/worse symptoms.

Time frame
Baseline only
3

PROMIS Depression - Short Form 8a

A patient-reported outcome (PRO) measure assessing symptoms of depression. Scores range from 8 to 40, with higher scores indicating more/worse symptoms.

Time frame
Baseline only
4

PROMIS Sleep - Short Form 8a

A patient-reported outcome (PRO) measure assessing symptoms of sleep disturbance. Scores range from 8 to 40, with higher scores indicating more/worse symptoms.

Time frame
Baseline only

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Missouri-Columbia

Lead sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Source ClinicalTrials.gov
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