- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00827762
Behavioral Effects of Kuvan in Children With Mild Phenylketonuria
Study Overview
Detailed 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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60614
- Northwestern University/Children's Memorial Hospital
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Missouri
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Columbia, Missouri, United States, 65211
- University of Missouri
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St. Louis, Missouri, United States, 63130
- Washington University
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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 Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Phenylketonuria
Individuals with mild phenylketonuria/hyperphenylalanemia who are beginning treatment with Kuvan.
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20/mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Behavior Rating Inventory of Executive Function (BRIEF)
Time Frame: baseline, 4-week follow-up, 24-week follow-up
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baseline, 4-week follow-up, 24-week follow-up
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Behavior Assessment System for Children - Second Edition (BASC-2)
Time Frame: baseline, 4-week follow-up, 24-week follow-up
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baseline, 4-week follow-up, 24-week follow-up
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Conners 3rd Edition (Conners 3)
Time Frame: baseline, 4-week follow-up, 24-week follow-up
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baseline, 4-week follow-up, 24-week follow-up
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Conners Continuous Performance Test II Version 5 (CCPT-II Version 5)
Time Frame: baseline, 4-week follow-up, 24-week follow-up
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baseline, 4-week follow-up, 24-week follow-up
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Matrix Reasoning subtest of the Wechsler Abbreviated Scale of Intelligence (WASI)
Time Frame: baseline, 4-week follow-up, 24-week follow-up
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baseline, 4-week follow-up, 24-week follow-up
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Collaborators and Investigators
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.
- 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.
- 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. doi: 10.1037//0894-4105.15.2.221.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MildPKU/Kuvan/White
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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