Classical Phenylketonuria(PKU)
Conditions
Brief summary
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND). The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers.
Interventions
None listed
Sponsors
BioMarin Pharmaceutical
Stanford University
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Sub-study Inclusion criteria same as main study: * ≥ 8 years of age * Confirmed diagnosis of PKU * Willing to continue current diet (typical diet for the 3 months prior to study entry)unchanged while participating in the study * Willing and able to provide written, signed informed consent or in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures * Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study and for at least 30 days following the last dose of sapropterin dihydrochloride * Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or have had total hysterectomy * Willing and able to comply with all study procedures
Exclusion criteria
All other sub-study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine in vivo redox status in patients with classical phenylketonuria | — | The primary objective of this study is to determine in vivo redox status in patients with classical phenylketonuria enrolled in PKU-016, compared to historical normal controls, using: * Serial Tc99m-HMPAO SPECT brain imaging (baseline and 26 weeks); and * Blood redox biomarkers, including oxidized and reduced glutathione, tetrahydrobiopterin, ascorbate, alpha-tocotrienol, selenium, etc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare redox status with neuropsychological and neuro-cognitive symptoms | — | Compare redox status as determined by brain imaging and blood redox biomarkers to measures of neuropsychological and neuro-cognitive symptoms (ADHD, anxiety, depression and executive function) and global function using data collected as part of PKU-016 |
| Explore the utility of other blood redox biomarkers | — | Explore the utility of other blood redox biomarkers (e.g. NAD+/NADH, NADP+/NADPH, protein carbonyls) in determining level of oxidative stress. |
Outcome results
None listed