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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00986973
First received: September 28, 2009
Last updated: February 4, 2013
Last verified: February 2013

September 28, 2009
February 4, 2013
March 2010
July 2011   (final data collection date for primary outcome measure)
Brain PET scan to evaluate brain glucose metabolism before and after BH4 (KUVAN) therapy [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00986973 on ClinicalTrials.gov Archive Site
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 ]
Secondary endpoints will include the following: the change in blood Phe levels, the change in Phe tolerance • The change in neurodevelopmental tests [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Phenylketonuria
Drug: KUVAN (BH4)

All subjects will receive 20 mg/kg/day KUVAN. Before and 4 months after KUVAN therapy

  • FDG-PET imaging,
  • Neuropsychological tests,
  • Blood phenylalanine levels and
  • Dietary phenylalanine tolerance will be evaluated
Other Names:
  • KUVAN
  • BH4
Experimental: BH4( KUVAN)
Intervention: Drug: KUVAN (BH4)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
September 2011
July 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00986973
IRB 09-007154
Yes
Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
Not Provided
Principal Investigator: Can Ficicioglu, MD, PhD Children's Hospital of Philadelphia,University of Pennsylvania
Children's Hospital of Philadelphia
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP