We aim to develop an innovative personalized prognostic model for outcome of children with TBI, using a unique combination of demographic, pre-injury and clinical predictors. The value of innovative MRI techniques and promising machine learning…
ID
Source
Brief title
Condition
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcomes of the study are motor functioning (Movement-ABC2),
neurocognitive functioning (Wechsler Intelligence Test) and behavioral
functioning (Child Behavior Checklist and Teacher Report Form), which will be
used to construct an overall outcome score. Demographic, pre-injury and
clinical predictors will be prospectively registered, as well as outcome at 6
months post-injury. Magnetic resonance imaging (MRI) will be performed at 1
month post-injury in a subsample of the children with TBI (aged >=8 years, n =
150). Outcome will be defined by the level of functioning for the child*s
demographics and pre-injury functioning. This will be measured by an overall
outcome score that will be constructed in three steps. First, total scores on
each test for each outcome domain (motor, neurocognitive and behavioral
functioning) will be transformed to z-scores, where the z-score describes the
difference between each TBI patient*s score and the mean of the
demographically-matched control group. Second, we will further adjust these
z-scores for the influence of pre-injury functioning (parent reported
pre-injury behavioral functioning and family functioning) by adding these
variables as predictors to the linear regression analyses on each z-score
pertaining to an outcome domain. The demographic and pre-injury adjusted
z-scores will then be retrieved by extracting the standardized residuals of
these regression analyses. Lastly, the overall outcome score will be calculated
by the sum of the adjusted z-scores. Since children with high pre-injury
functioning and significant decrement in functioning can still perform in the
average range of the general population, the demographic and pre-injury
adjustment procedure will increase sensitivity of outcome prediction. The
overall outcome score is used for the sake of clinical usability, enabling the
development of one prognostic model for outcome in a range of relevant domains
of functioning. Thanks to its cumulative nature, the overall outcome score will
be sensitive to poor outcome across function domains. The prognostic model will
also be used to predict outcome in each function domain separately in order to
identify children with selective impairment.
Secondary outcome
• Health status (TBI group and control group): Health status will be assessed
as a reference standard, allowing to investigate the relevance of primary study
parameters for health status. We will use the Childhood Health Assessment
Questionnaire, measuring heath status as defined by disability in a range of
Activities of Daily Life.
• School functioning (TBI group and control group): School functioning will be
assessed as a secondary outcome measurement in the subsample of children
attending a primary school. CITO Pupil Monitoring System results will be used
to assess school functioning. Based on the expected age range of this group
(6-12 years), this information will be available for a subsample of (3,5*30=)
105 children with TBI. The size of this subsample allows to build a separate
highly relevant prediction model for school outcome with a maximum of 7
predictors.
• Brain structure and function (TBI group only): Brain structure and function
will be assessed in children with TBI in order to investigate the (1) value of
innovative MRI for prognostic purposes and (2) neuroanatomical and
neurophysiological mechanisms that underlie neurocognitive impairment and daily
life problems. Brain structure and function will be measured using MRI
sequences.
• Specific neurocognitive functioning (TBI group and control group): Specific
neurocognitive functioning will be assessed in order to investigate the
neurocognitive mechanisms that underlie daily life problems and will be
measured using the Emma Toolbox for Computerized Neurocognitive Testing;
• Quality of life (TBI group and control group): Quality of life will be
measured using the EQ-5D questionnaires for children and adults.
• Brain function (TBI and control group): Resting state brain activity in
children will be assessed in order to investigate (1) the E-I balance in
children following TBI, (2) assess its value towards explaining the
heterogeneity in functional outcome. Brain function will be assessed using
resting state EEG.
Background summary
Traumatic brain injury (TBI) is the leading cause of death and disability in
children. TBI can cause poor outcome in crucial function domains, including
motor, neurocognitive and behavioral functioning. However, large differences
exist between patients, generated by the complex interplay between demographic
factors, pre-injury functioning and clinical characteristics. Available
clinical prediction tools are insufficient to account for the multifactorial
differences in outcome and the complex interplay between predictors. Outcome
prediction in children with TBI falls short, preventing clinicians to tailor
medical decision making to the child*s individual risk profile. This
contributes to overtreatment (i.e. unnecessary follow-up) and undertreatment
(i.e. undetected impairment).
Study objective
We aim to develop an innovative personalized prognostic model for outcome of
children with TBI, using a unique combination of demographic, pre-injury and
clinical predictors. The value of innovative MRI techniques and promising
machine learning algorithms will be investigated for prognostic purposes.
Additional goals are to explore neurocognitive and neural mechanisms that
contribute to poor outcome after paediatric TBI.
Study design
Observational controlled longitudinal study
Study burden and risks
TBI group:
The study procedures are associated with minimal risk. Parental questionnaires
assessing demographic characteristics and premorbid child and family
functioning will be administered shortly after admission of the child to the
hospital (estimated duration: 30 minutes). At one month post-injury, a sample
of 150 children aged >=8 years will revisit the hospital for magnetic resonance
investigation (estimated duration: max. 1.5 hour). At six months post-injury,
children (with at least one supervising parent) will revisit the hospital for
outcome measurement (estimated duration: max. 3.5 hours). Altogether, the child
and parent will visit the hospital twice (once if no MRI scan is made) in
addition to regular care. The total duration of study procedures is 5 hours for
children and 1-1.5 hour for parents (excluding 3.5 hours waiting time for
parents). Given the specific effects of TBI on (the post-injury development of)
children, it is crucial that this study is performed in a sample including
minors with TBI.
Control group:
The study procedures are associated with minimal risk. The outcome measurements
will also be executed for children in the control group during one appointment
with an estimated duration of max. 3.5 hours. The control group of typical
developing children will be used as a reference group for the TBI group and is
necessary to elucidate the impact of TBI on outcome measures, as corrected for
age, sex and socio-economic status. Standardized population norms are available
for some of the outcome measures, but these norms are only standardized for age
while it is well-known that other demographic characteristics can have a
considerable influence on child functioning. More specifically, children with
low socio-economic status are over-represented in the TBI population, while
socioeconomic status is known to have a strong influence on the impact and
recovery of TBI. Therefore, the confounding influence of socio-economic status
needs to be controlled for the construction of a valid and reliable
personalized prognosis, which cannot be done using age-standardized population
norms. This justifies the need to include a demographically matched typically
developing control group in the current study.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for the TBI group will be:
1. 4-18 years;
2. Fluent Dutch speaker;
3. Inhabitant of The Netherlands;
4. Hospital admission for mild to severe TBI.
5. No documented and/or parent-reported
diagnosis of a neurological disorder (other than TBI).
Inclusion criteria for the control group will be:
1. 4-18 years;
2. Fluent Dutch speaker;
3. Inhabitant of The Netherlands;
4. No documented and/or parent-reported
diagnosis of a neurological disorder (among which TBI).
Exclusion criteria
Participants who meets any of the following criteria will be excluded from
participation in this study:
1. Absence or withdrawal of written informed consent;
2. Severe motor disability that interferes with outcome assessment at time of
assessment;
3. Inability to comprehend testing instructions at time of assessment;
4. Somatic disorders unrelated to TBI and possibly affecting the outcome
assessments at time of assessment.
Design
Recruitment
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL71283.018.19 |
| OMON | NL-OMON21973 |