To establish the test-retest reliability of the 13C-PBT for measuring Phe hydroxylation in patients with PKU.
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The test-retest reliability of the 13C-PBT for measuring Phe hydroxylation,
expressed as the intraclass correlation coefficient (ICC).
Secondary outcome
- The relationship between Phe hydroxylation as measured by the 13C-PBT and the
genotypic phenotype values (GPV), as a measure of disease severity.
- A description (mean with 95% confidence interval) of the outcomes of the
13C-PBT in healthy persons.
Background summary
Phenylketonuria (PKU) is an inborn error of amino acid metabolism that affects
the hydroxylation of phenylalanine (Phe). To avoid severe neurological
complications associated with high blood Phe concentrations, it is necessary to
follow a lifelong treatment focused on keeping blood phenylalanine
concentrations within target range. While a dietary intervention that limits
Phe intake has been the mainstay of treatment for the last decades, recent and
upcoming treatment options are focussing on improving the patient*s capability
to metabolize Phe. These new treatments include cofactor treatment with
tetrahydrobiopterin and sepiapterin, but also therapeutic liver repopulation
and gene therapy. Assessing the effectiveness of such treatments is important
for research and patient care, and can, in theory, relatively easily be done
using a 13C-Phe breath test (13C-PBT). This test is based on quantifying the
conversion of 13C-Phe into 13C-Tyr by measuring 13CO2 in breath samples. While
this method has been described several times in the literature, no research has
yet focused on examining the test-retest reliability of the 13C-PBT in PKU
patients under stable conditions (e.g. without intervention), although this is
vital for evaluating the effect of a certain treatment using this test.
Study objective
To establish the test-retest reliability of the 13C-PBT for measuring Phe
hydroxylation in patients with PKU.
Study design
This is an observational study consisting of three parts:
- Part A: healthy volunteers > 16 years will undergo the 13C-PBT to optimize
the protocol for part B.
- Part B: PKU patients > 16 years will undergo the 13C-PBT twice to establish
the within-subject variation of Phe hydroxylation as measured by the 13C-PBT.
- Part C: PKU patients < 16 years will undergo the 13C-PBT twice to establish
the within-subject variation of Phe hydroxylation as measured by the 13C-PBT.
Part C will only take place in case analyses from part B suggest that the
test-retest reliability is at least moderate (defined as an intraclass
correlation coefficient > 0.40).
Study burden and risks
We assess that the burden of this study is low and the risks are minimal.
Participants in study part A will visit the UMCG once and will undergo the
13C-PBT once as well. Participants in study part B and C will visit the UMCG
twice, will undergo the 13C-PBT twice, will make six bloodspots, and will give
three samples of blood in total. Furthermore, participant in part B and C will
be instructed to make a dietary adjustment on the day of the 13C-PBT and to
make a blood spot on the following day. Since this is not a therapeutic study,
there are no direct benefits for the participants. There are however potential
benefits from the information gained from this study, as this study will be
essential for using the 13C-PBT to determine the effect of different (future)
treatment options in individual patients with PKU. Because we expect that the
13C-PBT will also be relevant for the care of children with PKU, it is
necessary to also include patients < 16 years to investigate and confirm our
outcomes in this age category.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
Part A (healthy adult volunteers)
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- At least 16 years old.
Part B (adults with PKU)
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- At least 16 years old.
- Diagnosed with PKU.
- Known genetic mutation of the PAH gene.
- Not receiving pharmacological treatment with BH4.
- Able to comply with the study protocol as assessed by their treating
physician (e.g. being able to comply with fasting overnight and remain rested
during the 13C-PBT).
- For females: a regular menstrual cycle (of approximately 4 weeks) OR
post-menopausal.
To be able to reach our secondary objective, it is necessary to include
patients with different phenotypes. Phenotypes of PKU patients can be expressed
by their genotypic phenotype values (GPV), which is a numerical representation
of PAH activity (and thus disease severity) that depends on the genotype of the
patient. An online database (http://www.biopku.org) provides GPVs for almost
all different genotypes (15). Of the 20 patients to be included in part B, we
aim to include >= 5 patients with classic PKU (GPV: 0-2.7), >= 5 patients with
mild PKU (GPV: 2.8-6.6), and >= 5 patients with mild hyperphenylalaninemia (GPV:
6.7-10.0).
Part C (children with PKU)
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- >= 6 years and <16 years old.
- Diagnosed with PKU.
- Known genetic mutation of the PAH gene.
- Not receiving pharmacological treatment with BH4.
- Able to comply with the study protocol as assessed by their treating
physician (e.g. being able to comply with fasting overnight and remain rested
during the 13C-PBT).
- For females: a regular menstrual cycle (of approximately 4 weeks) OR
pre-menarchic.
Similar to part B, we aim to include >= 5 patients with classic PKU (GPV:
0-2.7), >= 5 patients with mild PKU (GPV: 2.8-6.6), and >= 5 patients with mild
hyperphenylalaninemia (GPV: 6.7-10.0).
Exclusion criteria
Part A, B and C
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Pregnancy or wishing to become pregnant.
- Known liver and/or kidney dysfunction.
- Use of medication that may influence liver and/or kidney function.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71868.042.20 |