The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)

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.

Study Overview

• Status: Completed
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: Sapropterin

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 Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • University of Missouri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic for phenylketonuria. Columbia, Missouri, community for control.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Healthy individuals without phenylketonuria (PKU).
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: Kuvan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
functional magnetic resonance imaging of the brain	baseline, 4 week, & 6 month follow-up

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Collaborators: BioMarin Pharmaceutical
• Investigators: Principal Investigator: Shawn E Christ, Ph.D., University of Missouri-Columbia

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Principal Investigator's Laboratory Website

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: August 21, 2009
• First Submitted That Met QC Criteria: August 21, 2009
• First Posted (Estimate): August 24, 2009

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: January 2, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: cognition; brain; sapropterin; Kuvan
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: PKU/Kuvan/Christ