Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia
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.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia|
- Standard deviation of blood phenylalanine level (sdPHE) [ Time Frame: 24 hour period ]16 to 17 blood phenylalanine levels will be measured over 24 hours. The standard deviation of those measurements will be the sdPHE.
- Peak phenylalanine level [ Time Frame: 24 hour ]The highest blood phenylalanine level in the 24 hour period
- peak phenylalanine / tyrosine ratio [ Time Frame: 24 hours ]The highest blood phenylalanine / tyrosine ratio, with phenylalanine and tyrosine measured on the same sample
|Study Start Date:||May 2013|
|Study Completion Date:||December 2015|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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 <12 years and 120 - 600 umol/L for age ≥ 12 years.
Target 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 <12 years and 120 - 600 umol/L for age ≥ 12 years.
Subjects on Kuvan(TM) (any dose for at least 3 months with no dosage change for most recent 1 month) ± diet therapy
Subjects with non-PKU hyperphenylalaninemia (maximum phenylalanine level 120 - 599 umol/L on no therapy).
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01869972
|McMaster Children's Hospital|
|Hamilton, Ontario, Canada, L8S 4J9|
|Children's Hospital of Eastern Ontario|
|Ottawa, Ontario, Canada, K1H 8L1|
|Principal Investigator:||Murray Potter, MD||Hamilton Health Sciences Corporation|