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

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Phenylketonuria	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 Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	20 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
Study Start Date :	August 2009
Actual Primary Completion Date :	August 2010
Actual Study Completion Date :	August 2011

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. functional magnetic resonance imaging of the brain [ Time Frame: baseline, 4 week, & 6 month follow-up ]

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	6 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

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

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.

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Missouri
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

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Principal Investigator's Laboratory Website 

Publications:

Christ SE, Steiner RD, Grange DK, Abrams RA, White DA. Inhibitory control in children with phenylketonuria. Dev Neuropsychol. 2006;30(3):845-64.

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.

Responsible Party:	Shawn Christ, Prof Assoc, Psychological Sciences, University of Missouri-Columbia
ClinicalTrials.gov Identifier:	NCT00964236 History of Changes
Other Study ID Numbers:	PKU/Kuvan/Christ
First Posted:	August 24, 2009
Last Update Posted:	January 4, 2018
Last Verified:	January 2018

Keywords provided by Shawn Christ, University of Missouri-Columbia:

sapropterin; Kuvan; cognition; brain

Additional relevant MeSH terms:

Phenylketonurias; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors	Genetic Diseases, Inborn; Metabolic Diseases; Verapamil; Anti-Arrhythmia Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents