Sapropterin in Individuals With Phenylketonuria

• Status: Completed
• Trial end date: 2018-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Investigators at Washington University will examine the effects of sapropterin (Kuvan) on brain and cognition in individuals with phenylketonuria (PKU) using neuropsychological and neuroimaging procedures. Sapropterin is a medication developed by BioMarin Pharmaceutical Inc. that is approved by the FDA for treatment of patients with PKU to reduce phenylalanine (Phe) levels. Patients beginning treatment with sapropterin as standard clinical care will be enrolled in the study. As a first step, patients with PKU will receive baseline neuropsychological and neuroimaging evaluations 1 day prior to beginning treatment with sapropterin. Screening for response to sapropterin will occur over 4 weeks. At the end of 4 weeks, response to sapropterin will be reviewed. Patients with a reduction of ≥ 20% in blood Phe (i.e., responders) will receive follow-up neuropsychological and neuroimaging evaluations after 6 months of treatment with sapropterin. Patients (both responders and nonresponders) will receive long-term follow-up neuropsychological and neuroimaging evaluations 3 to 5 years after initial enrollment in the study.

The focus of neuropsychological testing will be executive abilities, as these abilities are particularly susceptible to disruption in individuals with PKU. We hypothesize that improvements in these abilities will occur following treatment with sapropterin. For neuroimaging assessments, structural magnetic resonance imaging (MRI) will permit evaluation of changes in the structure and volume of the gray and white matter of the brain, whereas diffusion tensor imaging (DTI) will permit evaluation of microstructural white matter integrity.

• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: BioMarin Pharmaceutical; University of Missouri-Columbia
• Treatments: Verapamil

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 sapropoterin.

• For phenylketonuria,phenylalanine level greater than or equal to 450μmol/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.