Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy (PKU)
The aim of this pilot study is to determine if there are any changes in brain glucose metabolism in the gray matter of patients with Phenylketonuria (PKU) and whether administration of KUVAN (BH4) therapy can improve such deficits.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Pilot Study of FDG PET Findings in Patients With Phenylketonuria Before and After BH4 Supplementation|
- Brain PET scan to evaluate brain glucose metabolism before and after BH4 (KUVAN) therapy [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Secondary endpoints will include the following: the change in blood Phe levels, the change in Phe tolerance, and the change in neurodevelopmental tests [ Time Frame: 4 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2010|
|Study Completion Date:||September 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
|Experimental: BH4( KUVAN)||
Drug: KUVAN (BH4)
All subjects will receive 20 mg/kg/day KUVAN. Before and 4 months after KUVAN therapy
Phenylketonuria (PKU) is an autosomal recessive disorder resulting from a deficiency of phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Phenylalanine hydroxylase is one of the three aromatic amino acid hydroxylases that utilizes tetrahydrobiopterin (BH4) as cofactor. The published reports indicate that there is altered energy metabolism in the brain of patients with PKU. Phenylalanine and its metabolites appear to impair several aspects of brain energetics including: (1) Inhibition of glucose uptake; (2) diminished glycosylation of cytoskeletal proteins; (3) Inhibition of pyruvate kinase; and (4) reduced flux through the glycolysis. Studies in vivo with magnetic resonance spectroscopy have demonstrated phenylalanine-responsive abnormalities in cerebral energy metabolism.
PET scanning with fluorodeoxyglucose (FDG-PET) is a non-invasive method that measures regional glucose metabolic rate with high resolution and absolute quantitation. To date this technology has been used only for single case reports or the investigation of white matter abnormalities in small numbers of patients with PKU.
The aim of this pilot study is to determine if there are any changes in brain glucose metabolism in the gray matter of patients with PKU and whether KUVAN (BH4) can improve such deficits. This study will also elucidate the relationship between hyperphenylalaninemia, phenylalanine intake in diet, altered brain glucose handling and the neurocognitive profile of the patients with PKU before and after KUVAN therapy.
|United States, Pennsylvania|
|Children's Hospital of Philadelphia, Section of Metabolism,PKU program|
|Philadelphia, Pennsylvania, United States, 19106|
|Principal Investigator:||Can Ficicioglu, MD, PhD||Children's Hospital of Philadelphia,University of Pennsylvania|