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

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Disease Information

Descriptive Information
Brief Title † Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy
Official Title † A Pilot Study of FDG PET Findings in Patients With Phenylketonuria Before and After BH4 Supplementation
Brief 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 KUVAN (BH4) 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. 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.
Study Phase N/A
Study Type † Interventional
Study Design † Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Primary Outcome Measure † Brain PET scan to evaluate brain glucose metabolism before and after BH4 (KUVAN) therapy
Secondary Outcome Measure † Secondary endpoints will include the following: the change in blood Phe levels, the change in Phe tolerance, and the change in neurodevelopmental tests
Condition † Phenylketonuria
Intervention † DrugKUVAN (BH4)
Study Arms / Comparison Groups BH4( KUVAN)
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 6
Start Date † March 2010
Completion Date September 2011
Primary Completion Date July 2011
Eligibility Criteria † Inclusion Criteria: 1. Males or females over the age of 18 years 2. Subject must be able to give independent informed consent 3. Girls must have a negative urine pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study. 4. Subject must have a confirmed diagnosis of PKU 5. Subjects with Phe levels over 10 mg/dL 6. Subjects naïve to BH4 (KUVAN) therapy or has not received KUVAN in the 6 months before screening Exclusion Criteria: 1. Pregnancy 2. Cognitive deficits resulting from physical trauma (e.g. subject with history of severe birth trauma). 3. Neurologic comorbidities including a history of a stroke or a seizure disorder. 4. Laboratory abnormalities that indicate clinically significant hepatic disease Aspartate aminotransferase (AST)> 2.0 times the upper limit of normal Alanine transaminase (ALT) > 2.0 times the upper limit of normal Prothrombin Time (PT) > 2.0 times the upper limit of normal Partial Thromboplastin Time(PTT)> 2.0 times the upper limit of normal 5. Subjects using medications such as steroids, insulin and glucagons that may interfere with the results of PET scan. 6. Subjects using medications that inhibit folate metabolism such as methotrexate 7. Subjects using medications known to affect nitric oxide-mediated vasorelaxation. 8. Subjects using Levodopa 9. Treatment with KUVAN in the past 6 months before study entry. 10. Treatment with any investigational product in the last 90 days before study entry
Gender Both
Ages 18 Years - 50 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries † United States
Administrative Information
NCT ID † NCT00986973
Organization ID IRB 09-007154
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Children's Hospital of Philadelphia
Collaborators ††
Investigators † Principal Investigator: Can Ficicioglu, MD, PhD, Children's Hospital of Philadelphia,University of Pennsylvania
Information Provided By
Verification Date February 2013
First Received Date † September 28, 2009
Last Updated Date February 4, 2013
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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