The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Sapropterin Individuals with phenylketonuria (PKU) who are beginning treatment with Kuvan (sapropterin). |
Drug: Sapropterin
Sapropterin (Kuvan) 20mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.
Other Names:
|
| Control Healthy individuals without phenylketonuria (PKU). |
Outcome Measures
Primary Outcome Measures
- functional magnetic resonance imaging of the brain [baseline, 4 week, & 6 month follow-up]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willing and able to provide informed consent or assent.
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Willing and able to comply with study procedures.
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Greater than or equal to 6 years of age.
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For phenylketonuria, intention of physician to prescribe sapropterin.
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For phenylketonuria, phenylalanine level greater than or equal to 300μmol/L.
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For phenylketonuria, negative pregnancy test if of childbearing potential.
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For phenylketonuria, willing to use contraception if sexually active.
Exclusion Criteria:
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Pregnant, breastfeeding, or planning to become pregnant during study.
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Use of investigational product less than 30 days prior to or during study.
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Concurrent condition that could interfere with participation or safety.
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Any condition creating high risk of poor compliance with study.
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Perceived to be unreliable or unavailable for study.
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Use of L-Dopa, methotrexate, or other drugs that inhibit folate metabolism.
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For phenylketonuria, known hypersensitivity to sapropterin or excipients.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Missouri | Columbia | Missouri | United States | 65211 |
Sponsors and Collaborators
- University of Missouri-Columbia
- BioMarin Pharmaceutical
Investigators
- Principal Investigator: Shawn E Christ, Ph.D., University of Missouri-Columbia
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Araujo GC, Christ SE, Steiner RD, Grange DK, Nardos B, McKinstry RC, White DA. Response monitoring in children with phenylketonuria. Neuropsychology. 2009 Jan;23(1):130-4. doi: 10.1037/a0013488.
- Christ SE, Steiner RD, Grange DK, Abrams RA, White DA. Inhibitory control in children with phenylketonuria. Dev Neuropsychol. 2006;30(3):845-64.
- PKU/Kuvan/Christ