Clinical trial NCT00964236: The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
Official title: The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Phenylketonuria
Keywords: sapropterin
Kuvan
cognition
brain
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2009-08-24
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Primary care clinic for phenylketonuria. Columbia, Missouri, community for control.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: functional magnetic resonance imaging of the brain
timeFrame: baseline, 4 week, & 6 month follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Shawn E Christ, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Christ SE, Steiner RD, Grange DK, Abrams RA, White DA. Inhibitory control in children with phenylketonuria. Dev Neuropsychol. 2006;30(3):845-64. doi: 10.1207/s15326942dn3003_5.
citation: 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.