Clinical Trial: MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria

Brief Summary: This is a study about the relationship of brain biomarkers with neuropsychological functioning in PKU. All participants will undergo MRI spectroscopy, will provide a blood specimen and will receive neuropsychological testing.

Detailed Summary: Despite newborn screening and early initiation of treatment, many adolescents and adults with PKU experience some degree of neuropsychological dysfunction or mood disturbances. Blood phenylalanine (Phe) levels and low levels of tyrosine (Tyr) only partially explain why some individuals with PKU have these difficulties and others do not. In this study, the investigators will use a new approach involving magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for measuring brain Phe (and other brain chemicals) in order to determine relationships between brain biomarkers and neuropsychological functioning and mood. Previously, brain Phe and Tyr could not be reliably measured by MRS methods, especially in concentrations likely to be found in individuals with treated PKU. This project will use an improved method for measuring brain Phe and Tyr. The investigators will use two-dimensional shift correlated magnetic resonance spectroscopy (COSY). COSY is a non-invasive method that allows for quantitative measurement of Phe, Tyr and other amino acids in the brain. This project has the potential to close one of the most important gaps in the knowledge of PKU, namely to define how PKU affects the brain. The aims of this study are to examine brain Phe and Tyr in individuals with PKU and in an age-matched healthy comparison group, and 2) determine the association of Phe and Tyr in distinct brain regions with measures of neuropsychological functioning and mood. Participants with PKU will receive 2 MRI scans with spectroscopy and the comparison group will receive 1 MRI scan with spectroscopy under fasting conditions. All participants will provide a blood specimen for blood amino acid determinations and will receive neuropsychological testing. The investigators will develop statistical models that can be applied in future studies to enhance understanding of PKU. This pilot study is important because it will provide evidence of the usefulness of COSY. COSY has the
Sponsor: Boston Children’s Hospital

Current Primary Outcome:

  • Neuropsychological functioning [ Time Frame: 1 day ]
    NIH Toolbox Cognitive Battery
  • Social/Emotional Outcome [ Time Frame: 1 day ]
    NIH PROMIS Questionnaires (Neuro QoL)
  • Blood Biomarkers [ Time Frame: 2 days ]
    Phenylalanine and Tyrosine (umol/L)
  • Brain Biomarkers [ Time Frame: 2 days ]
    Phenylalanine and Tyrosine (umol/L)


Original Primary Outcome: Same as current

Current Secondary Outcome: Intellectual Functioning [ Time Frame: 1 day ]

Full Scale IQ


Original Secondary Outcome: Same as current

Information By: Boston Children’s Hospital

Dates:
Date Received: March 22, 2017
Date Started: April 17, 2017
Date Completion: March 1, 2018
Last Updated: March 30, 2017
Last Verified: March 2017