Neurocognitive Outcomes in Mild Hyperphenylalaninemia (MHP)MHP Study

Phenylketonuria Clinical Trial

Official title: Neuropsychological and Quality of Life Outcomes in Untreated Adults With Mild Hyperphenylalaninemia (MHP)/Phenylketonuria (PKU) With Phenylalanine Levels Between 360 and 600 µmol/L Caused by Phenylalanine Hydroxylase (PAH) Deficiency.

Status Completed

Clinical Trial Summary

Phenylketonuria (PKU) is a genetic disorder known to cause severe reduction in intelligence and deficits in cognitive function; it is associated with an elevated level of Phenylalanine (Phe) in blood.

Newborn screening and early treatment with restricted protein diet supplemented by a formula of amino-acids will preserve intelligence. In those with the severe form treated from birth, some deficits that affect higher functions of the brain are seen.

Given this, there is disagreement about how milder forms of this disease should be managed and what level of Phe is safe to be left untreated.

We seek to assess whether higher Phe levels, between 360 and 600µmol/L, are safe with respect to preservation of intelligence and higher cognitive functions.

Clinical Trial Description

The following personal/medical information will be collected and reviewed:

• Evaluation of current and past medical history, including psychological treatment such as medication and counseling/therapy.

• Mutational analysis for each MHP subject

• Detailed history of educational, employment, relationship, and socioeconomic status/achievements as a measure of successful transition to adulthood

• Diet history, including past treatment with medical food or Sapropterin (Kuvan) for pre-conceptual and pregnancy Phe management

• All available untreated Phe levels, including newborn screening results (where possible) will be collated to calculate lifetime mean Phe level. Age at collections will be recorded separately for each MHP subjects to ensure inclusion of Phe levels beyond infancy

The following clinical investigations will be administered:

• Measurement of Phe and Tyrosine after an overnight fast, via blood spot using tandem mass spectrometry analysis. Blood spot collection will be done at the same time of day for all subjects.

• Physical exam, height and weight measurements

• Food Frequency Questionnaire assessment to estimate typical daily intake of natural protein.

• Self-Report Questionnaires:

• Behavior Rating Inventory of Executive Function (BRIEF)-A

• Beck Anxiety Inventory

• Beck Depression Inventory

• Quality of Life questionnaire

• Neuropsychological Tests assessed by a trained psychologist

An informant BRIEF-A report will be completed for each subject. To ensure consistency in rating, the same informant will be used where possible for the MHP subject and their sibling control (i.e. parents). These questionnaires will be mailed to the informants and returned to the study site via FedEx. ;

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Mild Hyperphenylalaninemia
• Phenylketonuria
• Phenylketonurias

• NCT number: NCT01924026
• Study type: Observational
• Source: The Hospital for Sick Children
• Status: Completed
• Phase: N/A
• Start date: September 2013
• Completion date: February 2016