Primary objective- To measure the effect of sapropterin on diurnal and day to day variations of blood phenylalanine concentrations.Secondary objective- To measure the effect of sapropterin on diurnal and day to day variations of blood tyrosine…
ID
Source
Brief title
Condition
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The mean standard deviations of the blood phenylalanine concentrations measured
four times a day of 2 consecutive days and once a day on the 6 consecutive days
of all participants compared between the sapropterin + diet treatment period
and the diet alone treatment period.
Secondary outcome
- The standard deviation of the blood tyrosine concentrations measured once a
day on 8 consecutive days of all participants compared between the sapropterin
+ diet treatment period and the diet alone treatment period.
- The mean standard deviations of the blood tyrosine concentrations measured
four times a day of 2 consecutive days of all participants compared between the
sapropterin + diet treatment period and the diet alone treatment period.
- The standard deviations of the blood phenylalanine/tyrosine ratios measured
once a day on 8 consecutive days of all participants compared between the
sapropterin + diet treatment period and the diet alone treatment period.
- The mean standard deviations of the blood phenylalanine/tyrosine
concentrations measured four times a day of 2 consecutive days of all
participants compared between the sapropterin + diet treatment period and the
diet alone treatment period.
Background summary
Patients with phenylketonuria (PKU) treated by diet only may have large
fluctuations in plasma concentrations of both phenylalanine (Phe) and tyrosine
(Tyr). Increased plasma phenylalanine, increased phenylalanine/tyrosine ratio,
and fluctuations in these values may negatively influence brain functions.
Apart from decreasing plasma phenylalanine concentrations, sapropterin may
influence positively plasma tyrosine concentrations, and by that also normalize
phenylalanine/tyrosine ratios. As a consequence, brain function may also be
improved. The question is whether sapropterin also stabilizes fluctuations of
especially phenylalanine. Some preliminary data suggest such stabilization of
phenylalanine concentrations. In addition, it is the question whether
sapropterin also stabilizes fluctuations of tyrosine, and the
phenylalanine/tyrosine ratio. There are no data to suggest or deny such an
influence on the fluctuations of tyrosine and the phenylalanine/tyrosine ratio.
The purpose of the study is to investigate the effect of sapropterin on
fluctuations of especially blood phenylalanine in children with PKU. The study
is hypothesis generating. Does sapropterin not only decrease the plasma
phenylalanine concentrations and increase the plasma tyrosine concentrations,
but also decreases the fluctuations in the plasma phenylalanine and tyrosine
concentrations and the phenylalanine/tyrosine ratio.
Study objective
Primary objective
- To measure the effect of sapropterin on diurnal and day to day variations of
blood phenylalanine concentrations.
Secondary objective
- To measure the effect of sapropterin on diurnal and day to day variations of
blood tyrosine concentrations.
- To measure the effect of sapropterin on diurnal and day to day variations of
blood phenylalanine/tyrosine ratio.
Study design
Open label randomized longitudinal crossover intervention study.
Intervention
16 PKU patients who use sapropterin as part of the treatment, males and females
4 to 12 years of age incl. and 18 years and above will be tested twice with
blood phenylalanine concentrations within therapeutic range. The two treatment
periods consists of a period of 8 consecutive days not using sapropterin (only
diet) and a period of 8 consecutive days using sapropterin + diet. Prior to
each treatment period, there will be a stabilization period of at least 15 days
in which patients already start with the treatment tested to achieve a stable
situation before testing. In the period without Kuvan®, a stricter diet with
respect to phenylalanine intake is prescribed to ensure comparable blood
phenylalanine concentrations. In both treatment periods the diet prescribed
will be comparable for total protein and energy intake, as well as for meal
frequency and fasting periods, but differentiating in the balance between
natural protein and protein substitute.
Study burden and risks
The study will be performed ambulatory. Parents/patients will sample blood at
home and participation in the study includes no extra visits to the hospital.
Instruction about the study will be realized by a research dietician at the
regular visits in the clinic, when preferred home visits and/or via mail and
telephone. In both study periods blood sampling is scheduled for the first two
days four times daily (7-8 am, 12-1 pm, 5-6 pm and bedtime) and once a day (7-8
am) on the six consecutive days thereafter, in total 28 samples per patient.
The sampling is done as routinely usual for the patient by finger puncture
collecting blood on filter paper. All samples of all participating patients
will be sent by mail to the UMCG laboratory Metabolic Diseases (Dr. R.
Heiner-Fokkema). During the sampling days 1 and 2 plus the day before the
sampling starts (in total 6 days) patients (or patient's* caretakers) perform a
detailed food record of all their food and beverages.
Both groups will enter the study at random. The stabilization period will be
used to create a stable situation before testing.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Males and females from 4 to 12 years of age incl. and 18 years and above.
- Diagnosed with phenylketonuria by newborn screening.
- Use of sapropterin as part of the treatment.
- Under good metabolic control; defined as 2/3 or 67% of the blood phenylalanine levels within target ranges during the last year.
Exclusion criteria
- Concomitant disease which may preclude the participation in the study in the judgment of the investigator.
- Intercurrent illness which might influence the blood phenylalanine levels.
- Concomitant medication as mentioned in the Kuvan® SPC.
- Known hypersensitivity to Kuvan® or its excipients.
- Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin.
- Non-compliance with study procedures in the judgement of the investigator.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2010-021343-41-NL |
| CCMO | NL45110.042.13 |
| Other | trialregister.nl |