The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01917344

Enrollment

Registered

2013-08-06

Start date

2013-08-31

Completion date

2014-06-30

Last updated

2015-06-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Phenylketonuria

Keywords

Phenylketonuria, MRI, Neuropsychological functioning, Neurological functioning, EEG

Brief summary

Newborn screening and early treatment prevent the most severe manifestations of phenylketonuria (PKU). However, executive functioning deficits, attention deficit disorder, slow processing speed, and visual-motor problems commonly occur. Many adults with this disorder also suffer depression and anxiety. Using advanced electroencephalogram (EEG) and magnetic resonance imaging (MRI) techniques, including novel MR spectroscopy (MRS) we hope to discover why this distinct constellation of deficits occurs in PKU. Adult subjects with PKU will undergo EEG and comprehensive MRI evaluations, including a novel method of MR spectroscopy to determine brain phenylalanine levels. In addition, they will receive neurological and neuropsychological examinations and dietary evaluation.

Interventions

OTHERMRI

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

1. Adult with classic PKU who has been seen at one of the hospitals collaborating in this study 2. Age 18-55 years 3. Medical Records available that include genotype and blood phenylalanine levels during the first 6 years of life. (We have over 300 patients with PKU with genotypes in our clinic, of whom about half are adults.) 4. Capable of providing informed consent 5. Able to undergo MRI procedures without sedating medication 6. Does not have metal implants 7. Not currently on Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trials. \-

Exclusion criteria

1. Mild PKU or mild hyperphenylalaninemia 2. Less than 18 years old or great than 55 years old 3. No medical records available for the first 6 years of life 4. No record of genotype 5. Not capable of providing informed consent 6. Not able to undergo MRI without sedating medication 7. Has metal implants 8. Currently taking Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trial \-

Design outcomes

Primary

Measure	Time frame	Description
Phenylalanine Level in the Brain as Determined by MR Spectroscopy and in Blood	During period of evaluation, approximately 8 hours	Brain Phe levels (umol/L) using MRI correlated spectroscopy and Blood Phe levels (umol/L) obtained on the same day.

Secondary

Measure	Time frame
Full Scale Intelligence Quotient (IQ)	During period of evaluation, approximately 8 hours
Electroencephalogram (EEG) Findings	During period of evaluation, approximately 8 hours
Volumetric MRI Findings	During period of evaluation, approximately 8 hours
Diffusion Tensor Imaging (DTI) Findings Through MRI	During period of evaluation, approximately 8 hours
Tremor as Determined Through Neurological Evaluation	During period of evaluation, approximately 8 hours

Countries

United States

Participant flow

Recruitment details

A recruitment letter was sent to adults with PKU who were not enrolled in another clinical trial.

Participants by arm

Arm	Count
Adults With PKU MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination MRI	10
Total	10

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Adults With PKU
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	10 Participants
Age, Continuous	29 years STANDARD_DEVIATION 5
Region of Enrollment United States	10 participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 10
serious Total, serious adverse events	0 / 10

Outcome results

Primary

Phenylalanine Level in the Brain as Determined by MR Spectroscopy and in Blood

Brain Phe levels (umol/L) using MRI correlated spectroscopy and Blood Phe levels (umol/L) obtained on the same day.