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Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia

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Disease Information

Descriptive Information
Brief Title † Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia
Official Title † Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia
Brief Summary Phenylketonuria (PKU) is a rare disease where the level of phenylalanine (one of the amino acids) in the body is greatly increased. High levels can cause brain damage, especially in babies and children. This brain damage can be prevented if a special low phenylalanine diet is started soon after birth. A new drug, sapropterin, can also lower phenylalanine levels in some patients. PKU therapy is monitored by measuring the blood phenylalanine every week, with the goal to keep the level within a target range. Recently, studies have suggested that the variation in the blood phenylalanine may be just as important as the absolute blood phenylalanine level for brain outcome. The investigators will look at the variation in blood phenylalanine level over 24 hours to see how much the level changes. The investigators will measure this in patients with typical PKU who are compliant with the diet and in patients who are not compliant with the diet. The investigators will also measure this in patients with "mild" PKU who do not usually have as high levels of phenylalanine. Finally, the investigators will see if patients on sapropterin have lower variation.
Detailed Description Phenylketonuria (OMIM 261600) results from the inherited deficiency of the enzyme phenylalanine hydroxylase, (PAH, Enzyme Classification 1.14.16.1). A deficiency of this enzyme leads to elevated blood and tissue levels of the amino acid phenylalanine upon exposure to normal amounts of dietary protein. The elevated phenylalanine in the brain is harmful to cognitive development, usually resulting in permanent severe mental retardation. Soon after the development of a special dietary treatment for PKU and of a simple screening test to detect elevated phenylalanine, newborn screening for PKU became widespread and early detection and treatment largely prevented the severe neurological effects of PKU. With population-based detection of hyperphenylalaninemia, it soon became apparent that there was significant biological variation of phenylalanine levels between patients (i.e. inter-individual biological variation) with phenylketonuria (PKU) and this now forms part of the classification system for hyperphenylalaninemia (i.e. benign hyperphenylalaninemia, mild, moderate or classical phenylketonuria). While variations of the classification system exist, most commonly "classical" PKU refers to individuals with plasma phenylalanine levels greater than 1200 µmol/L on an unrestricted diet. "Moderate" PKU refers to levels between 900 and 1200 µmol/L, while "mild" PKU refers to levels between 600 and 900 µmol/L. "Non-PKU" or "benign" hyperphenylalaninemia refers to phenylalanine levels less than 600 µmol/L on an unrestricted diet, that while greater than normal phenylalanine levels (
Study Phase N/A
Study Type † Observational
Study Design † Observational Model: Case Control, Time Perspective: Prospective
Primary Outcome Measure † Standard deviation of blood phenylalanine level (sdPHE)
Secondary Outcome Measure † Peak phenylalanine level
Condition † Phenylketonuria Hyperphenylalaninemia
Intervention †
Study Arms / Comparison Groups Wide PHE group Subjects prescribed diet alone to treat their PKU who have >1/3 of monitoring phenylalanine levels (with at least 3 levels measured) outside the target treatment range in the 6 months preceding enrolment. Target therapeutic range is 120 - 360 umol/L for age
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status †
Estimated Enrollment † 32
Start Date † May 2013
Completion Date December 2015
Primary Completion Date December 2015
Eligibility Criteria † Inclusion Criteria: • Subjects ≥4 years of age with hyperphenylalaninemia. Must have at least 1 documented blood phenylalanine level >600 µmol/L for study groups (Wide PHE, Target PHE, Kuvan groups) or >120 µmol/L for control group. Exclusion Criteria: - Significant cognitive impairment (IQ
Gender Both
Ages 4 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † Canada
Administrative Information
NCT ID † NCT01869972
Organization ID PKUvar-01
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Hamilton Health Sciences Corporation
Collaborators †† McMaster Children's Hospital
Investigators † Principal Investigator: Murray Potter, MD, Hamilton Health Sciences Corporation
Information Provided By
Verification Date August 2015
First Received Date † June 3, 2013
Last Updated Date August 17, 2015
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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