Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04993235 |
| Other study ID # |
RS2021_842 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 28, 2021 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
October 2023 |
| Source |
IRCCS Eugenio Medea |
| Contact |
Rosario Montirosso |
| Phone |
+39031877494 |
| Email |
rosario.montirosso[@]lanostrafamiglia.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Sotos Syndrome (SS) and Beckwith-Wiedemann Syndrome (BWS) are known as overgrowth syndromes
as they involve an excessive growth of the whole body or of specific body parts. Beyond their
primary physical problems, people with SS and BWS could present cognitive delay,
socio-emotional and social behavior difficulties. For the SS, previous research reported
impairments in specific neuropsychological domains and alterations of social behavior.
Nevertheless, a description of the neuropsychological and behavioral profile in developmental
age is still lacking. For the BWS, only in recent years alterations in social-cognitive
development and in social behavior have started to gain attention of clinicians and
researchers. However, no study has investigated the neuropsychological and behavioral
functioning of children and adolescents with BWS. In this light, this research project aims
at providing the first detailed description of the neuropsychological and behavioral profile
of children and adolescents with SS and BWS.
Moreover, patients with SS and BWS experience structural alterations of their bodies and are
early exposed to invasive diagnostical and medical procedures, which could interfere with the
development of body representation. Body representation starts forming early in life through
the integration of exteroceptive and interoceptive information, and plays a pivotal role in
the social-cognitive development. Given the changes occurring in puberty and the crucial
importance of body image in the relationship with peers, adolescence could be seen as a
critical period for studying body representation. Thus, this project would investigate body
representation at multiple levels (i.e. body image, body schema and interoceptive perception)
and evaluate their impact on social-cognitive abilities in adolescents with SS and BWS. It is
expected that both the clinical groups show alterations of body representation compared to
healthy peers, and that these alterations could associate with impairments in affect
recognition and regulation.
Description:
Background and Rationale Sotos Syndrome (SS) and Beckwith-Wiedemann Syndrome (BWS) are known
as overgrowth syndromes as they involve alterations in dimensions of the whole body or of
specific body parts. SS is characterized by advanced bone age, macrocephaly, characteristic
facies and cognitive delay. For the latter aspect, recent studies has described impairments
in specific neuropsychological domains and alterations of social behavior. However, this
evidence has been gathered in small and non-uniform samples, thus requiring further
investigation. Moreover, a description of the neuropsychological and behavioral profile of SS
in developmental age is still lacking. BWS is presented with macroglossia, exomphalos,
lateralized overgrowth and hyperinsulinism as cardinal features, and is often associated with
Wilms tumor and pathologies of internal organs. While the medical care of these primary
issues has greatly improved, recently alterations in social-cognitive development and in
social behavior have started to gain attention of clinicians and researchers. Nevertheless,
no study has investigated the neuropsychological and behavioral functioning of children and
adolescents with BWS.
Body representation is a complex, multi-faceted construct encompassing all the processes that
allow to perceive, to experience and to be aware of our body. Body representation starts
forming from the first months of life through the integration of exteroceptive and
interoceptive information, and plays a crucial role in social-cognitive development. Children
with SS and BWS experience structural alterations of their bodies and are early exposed to
invasive diagnostical and medical procedures, which could interfere with the development of
body representation. Given the changes occurring in puberty and the crucial importance of
body image in the relationship with peers, adolescence could be seen as a critical period for
body representation. Here, multiple levels of body representation (i.e., body image, body
schema and interoceptive accuracy) are investigated in adolescents with SS and BWS compared
to a control group of peers with typical development.
Aims The current study would provide a full description of the neuropsychological and
behavioral profile of children and adolescents with SS and BWS (Aim 1). Moreover, this study
protocol aims at investigating alterations of body representation at multiple levels, i.e.
body image, body schema and interoceptive perception, and at evaluating their impact on
social-cognitive abilities in adolescents with SS and BWS (Aim 2).
Methodologies This observational study involves two distinct assessment procedures, which may
be conducted in a single session or in two sessions.
For Aim 1, children with SS and BWS are administered selected subtests of the NEPSY-II, the
most adopted battery in developmental age in conditions of typical and atypical development.
The NEPSY-II provides a full description of the neuropsychological profile in six different
domains (Attention and executive functions, Language, Memory and learning, Sensorimotor
functions, Social Perception, Visuospatial skills). Colored and Standard Raven's Matrices are
also administered so as to obtain a reliable index of general intellectual functioning.
Moreover, a standardized assessment of academic skills is performed by means of specific
tests of the Memory and Transfert (MT) group for reading, comprehension and mathematic.
Lastly, parents are asked to fulfil a sheet collecting socio-demographic and anamnestic
information and two standardized questionnaires: the Child Behavior Check List (CBCL)
assessing the presence of emotional-behavioral problems, and the Autistic Quotient (AQ)
questionnaire assessing autistic traits related to five areas of functioning (social skills,
attention switching, attention to detail, communication and imagination). The entire
procedure is administered in a single session of approximately two hours and 30 minutes, in
which short breaks between activities (approximately 10 minutes) are allowed so as not to
overexert the child.
For Aim 2, adolescents (aged 11-18 years) with SS and BWS and healthy peers of the control
group are administered with a self-report questionnaire assessing body image, an ad hoc
created experimental task related to body schema, a virtual reality (VR) paradigm of
full-body illusion and two psychophysical tasks assessing interoceptive accuracy. The Body
Uneasiness Test (BUT) questionnaire consists of 34 items on a 1-5 Likert scale and allows for
the assessment of five dimensions related to body image (weight phobia, body image
preoccupation, compulsive self-monitoring, avoidance, and depersonalization). The
experimental task, administered through a computer, was developed according to recent studies
in literature that have assessed body schema changes in relation to peripersonal space and
interpersonal distance. Specifically, participants observe inanimate objects or avatars
approaching them. In one condition they have to judge whether they could easily reach the
objects/avatars (peripersonal space), in the other condition they have to indicate when the
object or avatar is perceived as "too close" (interpersonal distance). The full-body illusion
paradigm involves the use of a camera placed 2 meters behind the participant and of a VR head
mounted display. The back is touched by the experimenter and the image of this action is
replayed to the participant synchronously or with a time delay, thus creating an incongruence
between visual and haptic information.This paradigm induces an illusory sense of ownership of
the virtual body to be elicited more effectively than tasks focused on individual body parts,
and reliable as early as 7-8 year old. A short questionnaire adapted from the literature is
administered after each condition so as to assess the illusion in terms of sense of ownership
over the virtual body, sense of self location, and tactile sensations. In order to assess the
ability to perceive interoceptive signals (interoceptive accuracy), participants are
administerd a heartbeat perception task, in which they are asked to mentally count the number
of their own heartbeats over a certain period of time. Their responses are compared with
precise measurements of the heartbeats by means of a wrist-worn device that allows
noninvasive determination of heartrate by photoplethysmography. The procedure is repeated in
4 different time intervals administered in random order among participants, without giving
feedback on whether or not the responses are correct. In addition, a control task is proposed
in which the participant are asked to mentally count the seconds elapsed in 3 time intervals.
For both tasks, a visual analogic scale (VAS) is administered at the end of each time
interval to assess the degree of confidence in providing the response (0 = totally unsure to
10 = extremely confident). Lastly, in order to assess the difference in heartrate perception
at rest and in dynamic conditions, participants are administered the "Jumping Jack Paradigm,"
recently developed specifically for pediatric age (Schaan et al., 2019). For the baseline
condition, participants, sitting in a comfortable position, are asked to indicate on a VAS
how "loud" their heart rate feels. In the dynamic condition, participants are asked to jump
for 10 s and then indicate again on VAS how loud they feel their heartbeat is. The responses
provided on the VAS scales are compared with the heartrate recorded by the wrist-worn device.
The physical activity required is minimal, thus posing no danger to participants. At the same
time, this procedure facilitates the perception of the pulse and allows its assessment in an
ecological and intuitive way, limiting the impact of any cognitive difficulties. The entire
procedure is completed in approximately one hour and 30 minutes, inserting intervals of
approximately 10 minutes between tasks.
Analysis Plan For the first aim, all variables will be transformed into scaled or
standardized scores according to the normative tables for Italian samples, so as to compare
performances of the clinical groups with the age-matched population with typical development.
For each clinical group, the neuropsychological and behavioral profile will be estimated
using repeated-measures ANOVA models by entering the average scaled scores of each domain of
the NEPSY-II and the standardized scores obtained in the behavioral scales of the CBCL
questionnaire.
For the second aim, scores obtained in the five dimensions of the BUT questionnaire from the
clinical groups will be compared to those of the control group by means of two-tailed
Student's t-tests. For the body illusion task, the responses obtained at the questionnaire in
the different conditions will be considered.
For the heartbeat perception task, the difference between actual and reported heartbeats will
be transformed into an index of interoceptive accuracy according to previous literature. A
similar measure will be estimated for the temporal accuracy control task by calculating the
difference between actual and counted seconds.
For the experimental tasks, mixed ANOVA models will be used with both between-groups and
within-subject factors (social/non-social stimulus for the computer-based behavioral task,
synchronous and asynchronous stimulation for the full-body illusion, heart rate/seconds for
the psychophysical tasks).
Significant interaction effects will be explored with post-hoc tests. For all analyses, the
significance threshold will be set at p ≤ .05. Relationships between experimental task
variables and those derived from standardized tests and questionnaires will be analyzed using
Pearson's coefficient, correcting the significance threshold for the number of comparisons.
