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

This study has been withdrawn prior to enrollment.
(Withdrawn due to no funding)
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01650909
First received: July 24, 2012
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

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.


Condition Phase
Classical Phenylketonuria(PKU)
Phase 3

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical Phenylketonuria

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Determine in vivo redox status in patients with classical phenylketonuria [ Designated as safety issue: No ]

    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:
  • Compare redox status with neuropsychological and neuro-cognitive symptoms [ Designated as safety issue: No ]
    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 [ Designated as safety issue: No ]
    Explore the utility of other blood redox biomarkers (e.g. NAD+/NADH, NADP+/NADPH, protein carbonyls) in determining level of oxidative stress.


Biospecimen Retention:   Samples With DNA

Blood and urine will be collected to anaylze redox biomarkers


Enrollment: 0
Study Start Date: July 2012
  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Children 8+ and adults, any gender or ethic background, diagnosed with classical phenylketonuria and participating in PKU-016.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650909

Sponsors and Collaborators
Stanford University
BioMarin Pharmaceutical
Investigators
Principal Investigator: Gregory Enns, MD Stanford University
  More Information

Publications:
Sirtori LR, Dutra-Filho CS, Fitarelli D, Sitta A, Haeser A, Barschak AG, Wajner M, Coelho DM, Llesuy S, Belló-Klein A, Giugliani R, Deon M, Vargas CR. Oxidative stress in patients with phenylketonuria. Biochim Biophys Acta. 2005 Apr 15;1740(1):68-73.

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01650909     History of Changes
Other Study ID Numbers: Redox Sub-study of PKU-016
Study First Received: July 24, 2012
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on September 16, 2014