The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU) - Full Text View

Purpose

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	Intervention
Phenylketonuria	Drug: Sapropterin


Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Prospective
Official Title:	The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)

Resource links provided by NLM:

Genetics Home Reference related topics: N-acetylglutamate synthase deficiency argininosuccinic aciduria citrullinemia ornithine translocase deficiency phenylketonuria succinic semialdehyde dehydrogenase deficiency tetrahydrobiopterin deficiency

MedlinePlus related topics: Phenylketonuria

Drug Information available for: Sapropterin Sapropterin dihydrochloride

Genetic and Rare Diseases Information Center resources: Phenylketonuria Inborn Amino Acid Metabolism Disorder

U.S. FDA Resources

Further study details as provided by University of Missouri-Columbia:

Primary Outcome Measures:

functional magnetic resonance imaging of the brain [ Time Frame: baseline, 4 week, & 6 month follow-up ] [ Designated as safety issue: No ]


Enrollment:	20
Study Start Date:	August 2009
Study Completion Date:	August 2011
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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).

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


Ages Eligible for Study:	6 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00964236

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

Additional Information:

Principal Investigator's Laboratory Website This link exits the ClinicalTrials.gov site

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:	University of Missouri-Columbia
ClinicalTrials.gov Identifier:	NCT00964236 History of Changes
Other Study ID Numbers:	PKU/Kuvan/Christ
Study First Received:	August 21, 2009
Last Updated:	September 2, 2016
Health Authority:	United States: Institutional Review Board

Keywords provided by 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

ClinicalTrials.gov processed this record on September 29, 2016