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Behavioral Effects of Kuvan in Children With Mild Phenylketonuria

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ClinicalTrials.gov Identifier: NCT00827762
Recruitment Status : Terminated (Too few participants recruited within timeframe)
First Posted : January 23, 2009
Last Update Posted : December 5, 2013
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment
Phenylketonuria Drug: Kuvan

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 Design

Study Type : Observational
Actual Enrollment : 2 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Behavioral Effects of Kuvan in Children With Mild Phenylketonuria
Study Start Date : January 2009
Primary Completion Date : January 2010
Study Completion Date : January 2010

Groups and Cohorts

Group/Cohort Intervention/treatment
Individuals with mild phenylketonuria/hyperphenylalanemia who are beginning treatment with Kuvan.
Drug: Kuvan
20/mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.
Other Name: Sapropterin

Outcome Measures

Primary Outcome Measures :
  1. Behavior Rating Inventory of Executive Function (BRIEF) [ Time Frame: baseline, 4-week follow-up, 24-week follow-up ]

Secondary Outcome Measures :
  1. Behavior Assessment System for Children - Second Edition (BASC-2) [ Time Frame: baseline, 4-week follow-up, 24-week follow-up ]
  2. Conners 3rd Edition (Conners 3) [ Time Frame: baseline, 4-week follow-up, 24-week follow-up ]
  3. Conners Continuous Performance Test II Version 5 (CCPT-II Version 5) [ Time Frame: baseline, 4-week follow-up, 24-week follow-up ]
  4. Matrix Reasoning subtest of the Wechsler Abbreviated Scale of Intelligence (WASI) [ Time Frame: baseline, 4-week follow-up, 24-week follow-up ]

Eligibility Criteria

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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Primary care clinic for phenylketonuria.

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00827762

United States, Illinois
Northwestern University/Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65211
Washington University
St. Louis, Missouri, United States, 63130
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Washington University School of Medicine
BioMarin Pharmaceutical
University of Missouri-Columbia
Northwestern University
Oregon Health and Science University
Principal Investigator: Desiree White, Ph.D. Washington University School of Medicine
Principal Investigator: Dorothy K. Grange, M.D. Washington University School of Medicine
More Information

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00827762     History of Changes
Other Study ID Numbers: MildPKU/Kuvan/White
First Posted: January 23, 2009    Key Record Dates
Last Update Posted: December 5, 2013
Last Verified: December 2013

Keywords provided by Washington University School of Medicine:
executive abilities

Additional relevant MeSH terms:
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