The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
Summary
The objective of the study is to determine whether Kuvan™ (sapropterin) improves the strength of the functional connectivity between brain regions in individuals with PKU.
Description
The proposed study is designed to evaluate the hypothesis that functional connectivity may represent an early marker for neurocognitive improvements related to Kuvan treatment. As a first step in the study, 20 patients with PKU who are ≥ 6 years of age will receive baseline functional connectivity magnetic resonance imaging (fcMRI) evaluations before being treated with Kuvan™. Response to Kuvan™ will be monitored for 4 weeks. At the end of 4 weeks, response to Kuvan™ will be reviewed and all 20 patients will receive follow-up fcMRI evaluations. Fifteen patients with a reduction of ≥ 20% in blood phenylalanine will continue in the study and receive a third fcMRI evaluation at the end of 6 months of treatment with Kuvan™. For comparison purposes and to control for possible practice effects in repeated testing, a matched control group of 20 healthy individuals without PKU will used. All 20 of the control subjects will receive baseline and 4-week fcMRI evaluations; fifteen will receive a 6-month evaluation.
Study Design
Observational Model: Case Control, Time Perspective: Prospective
Conditions
Phenylketonuria
Intervention
Sapropterin (Kuvan)
Location
University of Missouri
Columbia
Missouri
United States
65211
Status
Enrolling by invitation
Source
University of Missouri-Columbia
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00964236
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:19:50-0400
Clinical Trials
Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
The primary objective of the study is to evaluate the proportion of responders [≥30% reduction from baseline in blood phenylalanine (Phe) level] to 20 mg/kg/day sapropterin dihydrochlori...
Sapropterin dihydrochloride (subsequently referred to as sapropterin) (Kuvan®) was approved by the FDA for the treatment of hyperphenylalaninemia in 2007. Preclinical and clinical studies...
Behavioral Effects of Kuvan in Children With Mild Phenylketonuria
The purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (PKU) who are taking Kuvan.
The investigators will investigate the effect of blood phenylalanine on Kuvan responsiveness in the same patients with PKU when their blood phenylalanine concentrations are altered by diet...
PKUDOS: PKU Demographic, Outcomes, and Safety Registry
The objective of this study is to evaluate the safety of long-term treatment with Kuvan.
PubMed Articles
Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (...
Non-invasive prenatal testing of pregnancies at risk for phenylketonuria.
Phenylketonuria (PKU) is a common metabolic disorder caused predominately by mutations in the phenylalanine hydroxylase (PAH) gene. The aim of the study was to design and validate the performance of a...
Phenylketonuria (PKU) is the most common form of amino acid metabolism disorders with autosomal recessive inheritance. The brain damage can be prevented by early diagnosis and a phenylalanine-restrict...
In phenylketonuria (PKU), during weaning, it is necessary to introduce a second stage phenylalanine (Phe)-free protein substitute (PS) to help meet non-Phe protein requirements. Semi-solid weaning Phe...
Untreated Phenylketonuria (PKU), one of the most common human genetic disorders, usually results in mental retardation. While a protein-restricted artificial diet can prevent retardation, dietary comp...
Medical and Biotech [MESH] Definitions
Phenylketonuria, Maternal
A condition occurring in untreated or partially treated females with PHENYLKETONURIA when they become pregnant. This may result in damages to the FETUS, including MICROCEPHALY; MENTAL RETARDATION; congenital heart disease; FETAL GROWTH RETARDATION; and CRANIOFACIAL ABNORMALITIES. (From Am J Med Genet 1997 Mar 3;69(1):89-95)
Phenylketonurias
A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).
Dihydropteridine Reductase
An enzyme that catalyzes the reduction of 6,7-dihydropteridine to 5,6,7,8-tetrahydropteridine in the presence of NADP+. Defects in the enzyme are a cause of PHENYLKETONURIA II. Formerly listed as EC 1.6.99.7.
Phenylalanine Hydroxylase
An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.
