Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy (PKU)
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Phenylketonuria |
Drug: KUVAN (BH4) |
| Study Type: | Interventional |
| 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 ]
| Enrollment: | 6 |
| Study Start Date: | March 2010 |
| Study Completion Date: | September 2011 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: BH4( KUVAN) |
Drug: KUVAN (BH4)
All subjects will receive 20 mg/kg/day KUVAN. Before and 4 months after KUVAN therapy
Other Names:
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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.
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Males or females over the age of 18 years
- Subject must be able to give independent informed consent
- 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.
- Subject must have a confirmed diagnosis of PKU
- Subjects with Phe levels over 10 mg/dL
- Subjects naïve to BH4 (KUVAN) therapy or has not received KUVAN in the 6 months before screening
Exclusion Criteria:
- Pregnancy
- Cognitive deficits resulting from physical trauma (e.g. subject with history of severe birth trauma).
- Neurologic comorbidities including a history of a stroke or a seizure disorder.
- 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
- Subjects using medications such as steroids, insulin and glucagons that may interfere with the results of PET scan.
- Subjects using medications that inhibit folate metabolism such as methotrexate
- Subjects using medications known to affect nitric oxide-mediated vasorelaxation.
- Subjects using Levodopa
- Treatment with KUVAN in the past 6 months before study entry.
- Treatment with any investigational product in the last 90 days before study entry
Contacts and Locations| 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 |
More Information
No publications provided
| Responsible Party: | Children's Hospital of Philadelphia |
| ClinicalTrials.gov Identifier: | NCT00986973 History of Changes |
| Other Study ID Numbers: | IRB 09-007154 |
| Study First Received: | September 28, 2009 |
| Last Updated: | February 4, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Children's Hospital of Philadelphia:
|
PKU BH4 KUVAN PET scan Neurodevelopment |
Additional relevant MeSH terms:
|
Phenylketonurias Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases |
ClinicalTrials.gov processed this record on June 17, 2013