Objective: The main objective of this study is to explore the executive, social-cognitive, and social functioning and behaviour of HT1 patients in relation to present and past tyrosine and phenylalanine levels, history of treatment and treatment…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: Neurocognitive tasks, measuring executive
functions (inhibition, working memory, cognitive flexibility) and social
cognition serve as study parameters. Questionnaires measuring executive and
social functioning and behaviour in daily life are also used. Historical and
concurrent tyrosine and phenylalanine concentrations are used as predictors
expecting significant differences between HT1 patients with high and low blood
levels, and between patients and controls.
Secondary outcome
Participants will perform an abbreviated version of the Wechsler Intelligence
Scale for Children (WISC) and Wechsler Adult Intelligence Scale (WAIS) with two
subtests: Block Design and Vocabulary.
Next to this timing and clinical symptoms at time of diagnosis and some
bloodresults will be gathered namely (all other amino acids (including
tryptophan), succinylacetone and NTBC concentration, serotonine, prolactin and
metanephrines (breakdown of noradrenaline and adrenaline))
Background summary
Rationale: Patients with Hereditary Tyrosinemia Type 1 (HT1; deficiency of
fumarylacetoacetate hydrolase, FAH) usually present with acute liver failure
during the first months of life, or (somewhat later) with renal tubular
dysfunction with rickets. Originally, HT1 was treated with a
tyrosine-phenylalanine restricted diet, usually followed by liver
transplantation. Since the discovery of
2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC), HT1 patients
are treated by NTBC and diet with good outcome with regard to liver disease and
renal problems. However, during the past years some preliminary evidence has
been provided that these patients are at risk of non optimal neurocognitive
outcome. It remains unclear whether these deficits are caused by the disease
itself, treatment with NTBC, the resulting high tyrosine, or the low
phenylalanine concentrations that are usually seen.
Study objective
Objective: The main objective of this study is to explore the executive,
social-cognitive, and social functioning and behaviour of HT1 patients in
relation to present and past tyrosine and phenylalanine levels, history of
treatment and treatment adherence, and to explore the abovementioned constructs
in relation to daily life functioning of HT1 patients (e.g. well-being, quality
of life, socio-economic status, friendships and/or relations).
Study design
Study design: Observational cross-sectional between-subjects control group
design. A group of HT1 patients will be tested with a wide range of
neuropsychological instruments, including executive functioning,
social-cognitive, and social functioning and behaviour, taking into account
treatment (drug and/or diet).
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Historical tyrosine and phenylalanine
concentrations are collected from the databases of the clinical centres and the
Dutch patient organization for metabolic diseases in children (Vereniging
Kinderen en Stofwisselingsziekte, VKS). Blood samples fall under normal
clinical visits and routine control and probably do not have to be taken more
often than the HT1 patients are used. Executive functions and social cognition
are examined by means of (computerized) tasks which will take a maximum of 2.5
hours. Questionnaires will be filled out to determine executive and social
functioning and behaviour in daily life. No physical and physiological
discomfort is expected, and no risks are associated with participation in the
tasks. The results of the study may help to further determine the
neurocognitive and social profile in HT1 patients.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
General inclusion criteria for recruitment of HT1 patients:
- Patients meet NIH-diagnostic criteria for Hereditary Tyrosinemia Type 1 (HT1)
- Patients are treated with NTBC alone or with a diet as well, or patients received orthotopic liver transplantation (OLT)
- Minimum age of 7 years at time of study
- IQ >= 80 (if unknown, this will be assessed)
- Patients have not participated in neuropsychological studies in the last 6 months
- Native speaker;General inclusion criteria for recruitment of controls:
- Controls are healthy
- Minimum age of 7 years at time of study
- IQ >= 80 (if unknown, this will be assessed)
- Controls have not participated in neuropsychological studies in the last 6 months
- Native speaker
Exclusion criteria
General exclusion criteria for recruitment of HT1 patients:
- Mental retardation that has been diagnosed by the clinical centre
- Neurological damage due to the disease, except for acute porphyria attacks
- Medical illnesses other than HT1 with known effects on cognitive and social functioning
- Not a native speaker;General exclusion criteria for recruitment of controls:
- Mental retardation that has been diagnosed by the clinical centre
- Medical illnesses with known effects on cognitive and social functioning
- Not a native speaker
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 | NL41405.042.12 |