NCT00986973

Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy

A Pilot Study of FDG PET Findings in Patients With Phenylketonuria Before and After BH4 Supplementation

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

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 Sapropterin (KUVAN) therapy can improve such deficits.

Detailed description

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. Positron Emission Tomography (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 Sapropterin (KUVAN) 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.

Conditions

• Phenylketonuria

Interventions

Type	Name	Description
DRUG	Sapropterin	All subjects will receive 20 mg/kg/day Sapropterin (KUVAN) for four months. Subjects will be examined with fluorodeoxyglucose positron emission tomography (FDG-PET) brain imaging, physical and neurological exam, blood tests for phenylalanine (Phe) and tyrosine levels, and neuropsychological testing before and 4 months after KUVAN therapy. Subjects Phe and tyrosine levels will be monitored weekly during the study and subjects will keep 3-day diet records to allow for calculation of Phe intake.

Timeline

• Start date: 2010-03-01
• Primary completion: 2011-07-01
• Completion: 2011-09-01
• First posted: 2009-09-30
• Last updated: 2015-06-08
• Results posted: 2015-05-12

Locations

1 site across 1 country: United States