Simple Breath Test to Examine Phenylalanine Metabolism

NCT02009904 | Completed DMC

• 1 other identifier: H12-01421
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Phenylketonuria(PKU)is a rare condition caused by the body's inability to properly breakdown an amino acid called phenylalanine(PHE), due to a missing enzyme, phenylalanine hydroxylase(PAH). When the enzyme is missing and/or not functioning properly, it increases the level of PHE in the body. High levels of PHE can cause severe brain damage or nerve damage unless the children are on a strict low PHE diet. A low PHE diet restricts the intake of protein rich foods and can pose a significant burden to both the patient and the family. Investigators at the University of British Columbia and British Columbia Children's Hospital will examine the phenylalanine metabolism in children with PKU using a simple breath test. Patients (5-18y) receiving standard clinical care at the BC Children's Hospital's Biochemical Diseases Clinic will be enrolled.The study will be conducted twice on each patient. Baseline measurements will be performed at the beginning of each study for each patient.The Physician in charge will then prescribe the standard dose of sapropterin dihydrochloride (Kuvan®) (20mg/kg/d) or otherwise as deemed appropriate by the physician-in-charge. The test will be repeated a week (minimum) after the beginning of treatment with the prescribed dose. The investigators propose that children who are responsive to sapropterin dihydrochloride (Kuvan®) will have increased 13CO2 in breath after treatment, and those who do not respond will have no change in the 13CO2 in the breath before and after treatment. As a comparison to the experimental group, age and gender matched healthy controls will also be studied. The test in healthy controls will be performed once without any intervention, and is only used as a comparative value.

Conditions

Phenylketonuria (PKU)

Keywords

PKU; Phenylketonuria; Phenylalanine; Children; Stable isotopes; Sapropterin dihydrochloride responsiveness

Outcome Measures

Primary Outcomes (1)

• 13C (carbon dioxide) production

  Breath samples are collected to measure 13C (carbon dioxide) production. Rate of carbon dioxide produced is measured at 60 minutes after the start of the study using an indirect calorimeter.

  2 hours (1 study day)

Study Arms (1)

Phenylketonuria (PKU); Healthy Controls

Children with PKU (5-18y); Age and Gender matched healthy subjects for comparison

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with PKU will be enrolled from the Biochemical Diseases clinic at the British Columbia Children's Hospital. Healthy controls will be enrolled from the community and will undergo screening for age and gender match.

You may qualify if:

• Study Subjects:
• Children (4-18y)diagnosed with PKU
• Parent(s) or guardian(s) willing and able to provide informed signed consent.
• Parent(s) or guardian(s) willing and able to comply with all study procedures
• Healthy controls:
• Healthy Children (4-18y) with no health condition
• Willing to go through an initial screening for age and gender match
• Parents or guardians willing and able to provide informed signed consent.
• Parents or guardians willing and able to comply with study procedures

You may not qualify if:

• Study Subjects:
• Children \< 4y of age diagnosed with PKU, as it may be challenging to collect breath samples and perform indirect calorimeter in very young children
• Children (4-18y)who are diagnosed with PKU, but are currently ill, with a fever, cold, vomiting or diarrhea
• Healthy controls:
• Healthy Children \< 4y of age , as it may be challenging to collect breath samples and perform indirect calorimeter in very young children.
• Healthy Children (4-18y), but are currently ill, with a fever, cold, vomiting or diarrhea.

Sponsors & Collaborators

• University of British Columbia: lead
• Rare Disease Foundation, Vancouver, Canada: collaborator

Study Sites (1)

Child & Family Research Institute

Vancouver, British Columbia, V5Z 4H4, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Breath samples from both groups (children with PKU and healthy controls)

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

• Rajavel Elango, Ph.D

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: December 9, 2013
• First Posted: December 12, 2013
• Study Start: January 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 24, 2020

Record last verified: 2020-09

Locations

CA (1)