Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia

NCT01869972 | Completed

• 1 other identifier: PKUvar-01
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Phenylketonuria; Hyperphenylalaninemia

Keywords

PKU; phenylketonuria; hyperphenylalaninemia; Kuvan; sapropterin

Outcome Measures

Primary Outcomes (1)

• Standard deviation of blood phenylalanine level (sdPHE)

  16 to 17 blood phenylalanine levels will be measured over 24 hours. The standard deviation of those measurements will be the sdPHE.

  24 hour period

Secondary Outcomes (2)

• Peak phenylalanine level

  24 hour

• peak phenylalanine / tyrosine ratio

  24 hours

Study Arms (4)

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).

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Metabolic and/or PKU clinic

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• McMaster Children's Hospital: collaborator
• Children's Hospital of Eastern Ontario: collaborator
• BioMarin Pharmaceutical: collaborator

Study Sites (2)

McMaster Children's Hospital

Hamilton, Ontario, L8S 4J9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Murray Potter, MD

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: June 5, 2013
• Study Start: May 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 11, 2015

Record last verified: 2015-12

Locations

CA (2)