The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical PKU

Study Overview
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Brief Summary
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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.

Official Title
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The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical Phenylketonuria

Conditions
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Classical Phenylketonuria(PKU)

Participation Criteria
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Eligibility Criteria
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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 Exclusion criteria same as main study: Has known hypersensitivity to sapropterin dihydrochloride or its excipients Subject breastfeeding at screening or planning to become pregnant (subject or partner) at any time during the study Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to the completion of all scheduled study assessments Received sapropterin dihydrochloride within 16 weeks of randomization • Have initiated or adjusted medication for treatment of ADHD, depression, or anxiety ≤ 8 weeks prior to randomization Taking medication known to inhibit folate synthesis (eg, methotrexate) Any condition requiring treatment with levodopa or any PDE-5 inhibitor Concurrent disease or condition that would interfere with study participation, compliance or safety as determined by the Investigator Any condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or not completing the study

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |