Clinical Trial: Sapropterin in Individuals With Phenylketonuria

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

Official Title: Effects of Sapropterin on Brain and Cognition in Individuals With Phenylketonuria

Brief Summary:

Investigators at Washington University will examine the effects of sapropterin (Kuvan) on brain and cognition in individuals with phenylketonuria (PKU) using neuropsychological and neuroimaging procedures. Sapropterin is a medication developed by BioMarin Pharmaceutical Inc. that is approved by the FDA for treatment of patients with PKU to reduce phenylalanine (Phe) levels. Patients beginning treatment with sapropterin as standard clinical care will be enrolled in the study. As a first step, patients with PKU will receive baseline neuropsychological and neuroimaging evaluations 1 day prior to beginning treatment with sapropterin. Screening for response to sapropterin will occur over 4 weeks. At the end of 4 weeks, response to sapropterin will be reviewed. Patients with a reduction of ≥ 20% in blood Phe (i.e., responders) will receive follow-up neuropsychological and neuroimaging evaluations after 6 months of treatment with sapropterin. Patients (both responders and nonresponders) will receive long-term follow-up neuropsychological and neuroimaging evaluations 3 to 5 years after initial enrollment in the study.

The focus of neuropsychological testing will be executive abilities, as these abilities are particularly susceptible to disruption in individuals with PKU. We hypothesize that improvements in these abilities will occur following treatment with sapropterin. For neuroimaging assessments, structural magnetic resonance imaging (MRI) will permit evaluation of changes in the structure and volume of the gray and white matter of the brain, whereas diffusion tensor imaging (DTI) will permit evaluation of microstructural white matter integrity.


Detailed Summary:

Investigators at Washington University will examine the effects of sapropterin (Kuvan) on brain and cognition in individuals with phenylketonuria (PKU) using neuropsychological and neuroimaging procedures. Sapropterin is a medication developed by BioMarin Pharmaceutical Inc. that is approved by the FDA for treatment of patients with PKU to reduce phenylalanine (Phe) levels. Patients beginning treatment with sapropterin as standard clinical care will be enrolled. As a first step, patients with PKU who are ≥ 6 years of age will receive baseline neuropsychological and neuroimaging evaluations 1 day prior to beginning their treatment with sapropterin. Screening for response to sapropterin (20mg/kg/day) will then occur over 4 weeks as standard care for enrolled patients. At the end of 4 weeks, response to sapropterin will be reviewed. Patients with a reduction of ≥ 20% in blood Phe (i.e., responders) will receive follow-up neuropsychological and neuroimaging evaluations after 6 months of treatment with sapropterin. Patients (both responders and nonresponders) will receive long-term follow-up neuropsychological and neuroimaging evaluations 3 to 5 years after initial enrollment in the study.

A matched control group of healthy individuals without PKU will receive baseline and follow-up neuropsychological and neuroimaging evaluations for comparison purposes and to control for possible practice effects in repeated neuropsychological testing.

The focus of neuropsychological testing will be executive abilities, as these abilities are particularly susceptible to disruption in individuals with PKU. Specifically, the focus of neuropsychological assessment will be working memory, strategic processing, and inhibitory control, as our research group has shown that each of these executive abilities is impaired in individuals with
Sponsor: Washington University School of Medicine

Current Primary Outcome: diffusion tensor imaging of the brain [ Time Frame: baseline & follow-ups ]

assesses functional white matter integrity


Original Primary Outcome:

  • Wechsler Abbreviated Scale of Intelligence [ Time Frame: baseline & 6 month follow-up ]
  • diffusion tensor imaging of the brain [ Time Frame: baseline & 6 month follow-up ]


Current Secondary Outcome:

  • n-back task [ Time Frame: baseline & follow-ups ]
    assesses working memory
  • recognition span task [ Time Frame: baseline & follow-ups ]
    assesses working memory
  • list learning task [ Time Frame: baseline & follow-ups ]
    assesses strategic processing
  • verbal fluency task [ Time Frame: baseline & follow-ups ]
    assesses strategic processing
  • go/no-go task [ Time Frame: baseline & follow-ups ]
    assesses inhibitory control
  • stimulus-response compatibility task [ Time Frame: baseline & follow-ups ]
    assesses inhibitory control
  • structural magnetic resonance imaging of the brain [ Time Frame: baseline & follow-ups ]
    assesses structural brain integrity
  • Wechsler Abbreviated Scale of Intelligence [ Time Frame: baseline & follow-ups ]
    assesses general intellectual ability


Original Secondary Outcome:

  • working memory n-back task [ Time Frame: baseline & 6 month follow-up ]
  • working memory recognition span task [ Time Frame: baseline & 6 month follow-up ]
  • strategic processing list learning task [ Time Frame: baseline & 6 month follow-up ]
  • strategic processing verbal fluency task [ Time Frame: baseline & 6 month follow-up ]
  • inhibitory control go/no-go task [ Time Frame: baseline & 6 month follow-up ]
  • inhibitory control stimulus-response compatibility task [ Time Frame: baseline & 6 month follow-up ]
  • structural magnetic resonance imaging of the brain [ Time Frame: baseline & 6 month follow-up ]


Information By: Washington University School of Medicine

Dates:
Date Received: August 1, 2008
Date Started: July 2008
Date Completion: July 2015
Last Updated: December 8, 2014
Last Verified: December 2014