Behavioral Effects of Kuvan in Children With Mild Phenylketonuria

Phenylketonuria Clinical Trial

Official title:

Behavioral Effects of Kuvan in Children With Mild Phenylketonuria

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00827762
• Other study ID #: MildPKU/Kuvan/White
• Status: Terminated
• Phase: N/A
• First received: January 21, 2009
• Last updated: December 3, 2013
• Start date: January 2009
• Est. completion date: January 2010

Study information

• Verified date: December 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (PKU) who are taking Kuvan.

Description:

Little research has been conducted to examine behavior and cognition in children with mild PKU/hyperphenylalanemia, but there is evidence of reductions in general intelligence (IQ) (Costello, 1994) and impairments in executive abilities (Diamond, 1994; Gassio, 2005) in this population. It is important to note that the phenylalanine levels of children with mild PKU are approximately equivalent to those of children with classical PKU whose phenylalanine levels have been managed through dietary control. In children with diet-treated PKU, impairments in behavior and cognition are well-documented, particularly in relation to executive abilities (Christ, 2006; White, 2001, 2002). Taken together, these findings suggest that children with mild PKU are at risk for behavioral and cognitive impairments, and it is possible that these impairments may be mitigated by lowering phenylalanine levels through treatment with Kuvan.

To investigate this issue, approximately 20 children with mild PKU from 6 to 18 years of age (inclusive) and their parents will participate in the study. The behavior and cognition of children with mild PKU will be assessed using the following methods: (1) Parents will complete inventories to rate the behavior and cognition of their children; (2) Older children will complete self-report inventories to rate their behavior and cognition; (3) Cognitive tasks assessing IQ and executive aspects of attention (i.e., sustained attention and inhibitory control) will be administered to all children.

The primary objectives are two-fold. First, we will determine if behavior and cognition are compromised in children with mild PKU prior to treatment with Kuvan (baseline). To accomplish this objective, we will administer measures of behavior and cognition that include normative data based on age. We hypothesize that children with mild PKU will have ratings and scores that are ≥ 1 standard deviation from the normative mean. Second, we will determine if behavior and cognition improve in children with mild PKU following treatment with Kuvan. To accomplish this objective, we will administer the same measures of behavior and cognition after 4 and 24 weeks of treatment with Kuvan(4-week and 24-week follow-ups, respectively). We hypothesize that the follow-up ratings and scores of children with mild PKU will improve by ≥ 0.5 standard deviation relative to their baseline ratings and scores.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

• Willing and able to provide informed consent and/or assent.

• Willing and able to comply with study procedures.

• Between 6 and 18 years of age, inclusive.

• Intention of physician to prescribe Kuvan.

• Phenylalanine levels between 360µmol/L and 600µmol/L, inclusive, when untreated with dietary restrictions.

• Negative pregnancy test if of childbearing potential.

• Willing to use contraception if sexually active.

Exclusion Criteria:

• Treatment with Kuvan within the past 6 months.

• 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.

• History of major medical disorder unrelated to phenylketonuria.

• Perceived to be unreliable or unavailable for study.

• Use of L-Dopa, methotrexate, or other drugs that inhibit folate metabolism.

• Known hypersensitivity to sapropterin or excipients.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

Drug:
• Kuvan
20/mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.

Locations

Country	Name	City	State
United States	Northwestern University/Children's Memorial Hospital	Chicago	Illinois
United States	University of Missouri	Columbia	Missouri
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University	St. Louis	Missouri

Sponsors (5)

Lead Sponsor	Collaborator
Washington University School of Medicine	BioMarin Pharmaceutical, Northwestern University, Oregon Health and Science University, University of Missouri-Columbia

Country where clinical trial is conducted

United States, 

References & Publications (3)

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

White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria. J Int Neuropsychol Soc. 2002 Jan;8(1):1-11. — View Citation

White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Deficits in memory strategy use related to prefrontal dysfunction during early development: evidence from children with phenylketonuria. Neuropsychology. 2001 Apr;15(2):221-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Behavior Rating Inventory of Executive Function (BRIEF)		baseline, 4-week follow-up, 24-week follow-up	No
Secondary	Behavior Assessment System for Children - Second Edition (BASC-2)		baseline, 4-week follow-up, 24-week follow-up	No
Secondary	Conners 3rd Edition (Conners 3)		baseline, 4-week follow-up, 24-week follow-up	No
Secondary	Conners Continuous Performance Test II Version 5 (CCPT-II Version 5)		baseline, 4-week follow-up, 24-week follow-up	No
Secondary	Matrix Reasoning subtest of the Wechsler Abbreviated Scale of Intelligence (WASI)		baseline, 4-week follow-up, 24-week follow-up	No