behavioral effects of kuvan in children with mild phenylketonuria

Conditions: Phenylketonuria

Summary: the purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (pku) who are taking kuvan.

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.

Eligibility criteria:
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.

Keywords: phenylketonuria kuvan sapropterin behavior cognition executive abilities attention