Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Hamilton Health Sciences Corporation
Sponsor:
Collaborators:
McMaster Children's Hospital
Children's Hospital of Eastern Ontario
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01869972
First received: June 3, 2013
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

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.


Condition
Phenylketonuria
Hyperphenylalaninemia

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • Standard deviation of blood phenylalanine level (sdPHE) [ Time Frame: 24 hour period ] [ Designated as safety issue: No ]
    16 to 17 blood phenylalanine levels will be measured over 24 hours. The standard deviation of those measurements will be the sdPHE.


Secondary Outcome Measures:
  • Peak phenylalanine level [ Time Frame: 24 hour ] [ Designated as safety issue: No ]
    The highest blood phenylalanine level in the 24 hour period

  • peak phenylalanine / tyrosine ratio [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The highest blood phenylalanine / tyrosine ratio, with phenylalanine and tyrosine measured on the same sample


Estimated Enrollment: 32
Study Start Date: May 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.
Kuvan(TM) group
Subjects on Kuvan(TM) (any dose for at least 3 months with no dosage change for most recent 1 month) ± diet therapy
Control group
Subjects with non-PKU hyperphenylalaninemia (maximum phenylalanine level 120 - 599 umol/L on no therapy).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Metabolic and/or PKU clinic

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 <70 or clinical judgment).
  • Pregnancy
  • Other specific PKU therapies, including enzyme replacement therapy or any amino acid supplement designed to block uptake or transport of phenylalanine (i.e. large neutral amino acid mixtures)
  • Any intercurrent illness within the previous 5 days (any of fever, vomiting, diarrhea, decreased intake, upper respiratory tract infection).
  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: NCT01869972

Locations
Canada, Ontario
McMaster Children's Hospital Recruiting
Hamilton, Ontario, Canada, L8S 4J9
Contact: Murray Potter, MD    905-521-2100 ext 73718    mpotter@hhsc.ca   
Contact: Amy Pender, MSc    905-521-2100 ext 73414    pendera@hhsc.ca   
Principal Investigator: Murray Potter, MD         
Children's Hospital of Eastern Ontario Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Michael Geraghty, MD    613-737-7600 ext 2180    mgeraghty@cheo.on.ca   
Principal Investigator: Michael Geraghty, MD         
Sponsors and Collaborators
Hamilton Health Sciences Corporation
McMaster Children's Hospital
Children's Hospital of Eastern Ontario
BioMarin Pharmaceutical
Investigators
Principal Investigator: Murray Potter, MD Hamilton Health Sciences Corporation
  More Information

No publications provided

Responsible Party: Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01869972     History of Changes
Other Study ID Numbers: PKUvar-01
Study First Received: June 3, 2013
Last Updated: June 4, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Hamilton Health Sciences Corporation:
PKU
phenylketonuria
hyperphenylalaninemia
Kuvan
sapropterin

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 July 20, 2014