Interindividual variability in brain vulnerability to elevated blood phenylalanine concentrations in PKU patients - pilot study on amino acid transport in fibroblasts as a representative of the blood-brain barrier

Withdrawn

• Conditions: Phenylketonuria; PKU; 10037008

• Registration Number: NL-OMON44921
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

In order to be eligible for participation in one of the defined study groups, for each specific study group, subjects should meet the following inclusion criteria:;Group 1:
- Subjects meet NIH-diagnostic criteria for phenylketonuria
- PKU treatment has been initiated after 6 months of age
- Being able to perform daily living activities without the help of specialized caregivers and/or defined IQ score > 80
- Aged >= 18 years;Group 2:
- Subjects meet NIH-diagnostic criteria for phenylketonuria
- PKU treatment has been initiated after 6 months of age
- Living in an institute for mentally retarded persons and/or defined IQ score < 50
- Aged >= 18 years;Group 3:
- Subjects meet NIH-diagnostic criteria for phenylketonuria
- Early- (within 1 month after birth) and continuously-treated
- > 75% of historical data on plasma phenylalanine concentrations below target levels (< 12 years of age: < 360 µmol/L; <= 12 years of age: < 600 µmol/L)
- Diagnosed with ADHD or an autism spectrum disorder
- Aged >= 8 years and to whom the procedure can well be explained ;Group 4:
- Subjects meet NIH-diagnostic criteria for phenylketonuria
- Early- (within 1 month after birth) and continuously-treated
- >67% of historical data on plasma phenylalanine concentrations below target levels (<12 years of age: <360 µmol/L; >=12 years of age: <600 µmol/L)
- Aged >=18 years ;Group 5:
- Aged >= 18 years

Exclusion Criteria

For each of the defined study groups, patients will be excluded in case of the following:;Group 1:
- IQ score < 80 after assessment;Group 2:
- IQ score > 40 after assessment;Group 4:
- Diagnosed with ADHD or an autism spectrum disorder;Group 5:
- Diagnosed with PKU
- ADHD or autism spectrum disorder
- Known disorder of amino acid transport

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoints of this study will include:<br /><br>-kinetic parameters (Km and Vmax values) for transport of phenylalanine across<br /><br>fibroblast membranes of subjects from the different study groups. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secundary endpoints of this study will include:<br /><br>-kinetic parameters (Km and Vmax values) for transport of tyrosine and<br /><br>tryptophan across fibroblast membranes of subjects from the different study<br /><br>groups.<br /><br>-expression of amino acid transporters in fibroblasts of subjects from the<br /><br>different study groups.<br /><br>-transport characteristics for phenylalanine and other large neutral amino<br /><br>acids will be determined in microvascular endothelial cells.<br /><br>-variances in genes involved in amino acid transport between subjects from the<br /><br>different study groups.</p><br>