Phenylketonuria
Conditions
Keywords
sapropterin, Kuvan, cognition, brain
Brief 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.
Detailed 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.
Interventions
DRUGSapropterin
Sapropterin (Kuvan) 20mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.
Sponsors
BioMarin Pharmaceutical
University of Missouri-Columbia
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to provide informed consent or assent. * Willing and able to comply with study procedures. * Greater than or equal to 6 years of age. * For phenylketonuria, intention of physician to prescribe sapropterin. * For phenylketonuria, phenylalanine level greater than or equal to 300μmol/L. * For phenylketonuria, negative pregnancy test if of childbearing potential. * For phenylketonuria, willing to use contraception if sexually active.
Exclusion criteria
* Pregnant, breastfeeding, or planning to become pregnant during study. * Use of investigational product less than 30 days prior to or during study. * Concurrent condition that could interfere with participation or safety. * Any condition creating high risk of poor compliance with study. * Perceived to be unreliable or unavailable for study. * Use of L-Dopa, methotrexate, or other drugs that inhibit folate metabolism. * For phenylketonuria, known hypersensitivity to sapropterin or excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| functional magnetic resonance imaging of the brain | baseline, 4 week, & 6 month follow-up |
Countries
United States
Outcome results
None listed