1. To identify biomarkers and methodologies (neuroimaging, eye tracking, cognition, biochemistry, proteomics, genomics, etc.) that can be used to stratify patient groups into more homogeneous subgroups and/or that predict clinical outcome of…
ID
Source
Brief title
Condition
- Communication disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Trajectory of clinical symptomatology over time and in relation to underpinning
cognitive and neurobiological abnormalities; identification of biomarkers that
link to symptomatology and/ or that can be used to stratify ASD samples and/or
to diagnose ASD, and/or serve as outcome markers.
Primary parameters are:
- Severity of ASD and comorbid symptoms (measured by questionnaires,
psychiatric observation (ADOS) and psychiatric developmental interview (ADI-R)
- Performance on neurocognitive tests
- Brain structure and functioning, as measured by MRI and EEG/ERPs
- Attention and social attention, as measured by eye-tracking technology
Secondary outcome
- Analyses of blood, urine, saliva, stool and hair samples
Background summary
Autism Spectrum Disorders (ASD) affect about 1 in 100 individuals and are
characterized by qualitative impairments in social interactions, communication,
and repetitive and restricted behaviours and interests, and abnormal sensory
processing. Currently, diagnosis is still solely based on behavioural
classification and there are no effective pharmacological treatments for the
core symptoms that improve the long-term outcome. The discovery of novel
treatments is a challenge because ASDs are clinically, etiologically and
biologically very heterogeneous. For example, clinical manifestations depend on
several factors, such as age and ability level. Cognitive deficits and
abnormalities in brain development/function are also likely to change over
development. Hence, some treatments may only be effective in certain subgroups
or at certain points in development. Recently, neuroimaging, eye-tracking and
electrophysiological markers have emerged as potential biomarkers to aid
clinical stratification of patients with ASD. However, this approach requires
comprehensive assessments of participants in studies with substantially larger
sample sizes than that included in any existing study to date.
This multi-centre study will follow-up a large cohort of previously enrolled
individuals. This includes approximately N=350 ASD participants that are
diverse in terms of age (6-30 years) and level of intellectual functioning, and
N=250 control participants. Our purpose is to identify cognitive and biological
markers that may aid in the reliable diagnosis of ASD and/ or serve as
stratification markers and/ or pharmacological treatment targets.
Study objective
1. To identify biomarkers and methodologies (neuroimaging, eye tracking,
cognition, biochemistry, proteomics, genomics, etc.) that can be used to
stratify patient groups into more homogeneous subgroups and/or that predict
clinical outcome of patients with ASD;
2. To examine how the clinical ASD phenotype and biomarker profile develop over
three time points through re-assessment after about 5 years after wave-2 by
using an accelerated longitudinal design.
Further.
3 To identify clinical measures that map on clinical outcome and quality of
life of patients with ASD;
4. To investigate the link between biochemical markers, brain structure and
function, cognition and clinical symptomatology;
5. To delineate a profile of neuro-cognitive abnormalities across different
cognitive domains in the ASD group, and ascertain whether abnormalities only
exist in certain sub-groups or at certain developmental levels;
6. To examine abnormalities in brain structure, function and cognition in
low-functioning individuals with ASD (IQ range: 50-69); a patient group with
the poorest outcome and for whom effective treatment is particularly urgent
7. Development and testing of new digital phenotypes concerning social
behaviour, activities and mood as potential new outcome measures
Study design
Multi-centre prospective observational cross-sectional and accelerated
longitudinal case-control design (with now 3 time points)
Study burden and risks
Typically, participants will be invited for a visit to the Radboudumc and
Donders Centre (Nijmegen) or the UMC Utrecht (Utrecht) for a one-day visit
(about 6 hours) for MRI scanning, EEG/ERP and eye-tracking assessments,
cognitive testing and completion of questionnaires. Depending on feasibility
and practical factors, the visit can also be split into two shorter visits.
We will collect blood by venapucture (10 ml). The completion of questionnaires
can be spread over 2 weeks, and can also be done in part on-line. The total
time for completing questionnaires will be 10 hours. We will reimburse the
participans and their parents for completing all measures.
All procedures are safe, and will be conducted by trained and skilled
personnel. All participants will already have participated in the previous
waves of the study.
We use a mock scanner to familiarize the participant with the MRI environment.
There are no immediate and direct benefits for participants. However,
establishing and validating biomarkers for ASD will facilitate developing and
testing new interventions, may uncover the pathophysiology of ASD, and or
improve diagnostic procedures and/or improve prediction of outcome and course.
This new knowledge may at the middle-long term benefit all persons with ASD and
their families.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
Having participated in LEAP-1 and/or LEAP-2; the criteria observed at wave-1
were:
ASD group:
1. Male or female aged 6-30 years with an established clinician diagnosis of
Autism Spectrum Disorder according to DSM-5 criteria;
2. Male or female with an IQ of 50 or above;
3. Able to participate and willing to give written informed consent;
(a) Where participants are their own legal guardian (i.e. aged 18 years and
older without intellectual disabilities and demonstrated capacity to consent),
written informed consent from the volunteer;
(b) Where participants are minors and/or do not have capacity to consent,
written informed consent from the parent or legal guardian; verbal assent from
the volunteer prior to each assessment; for adolescents and adults without
capacity to consent: additional written assent from the volunteer (easy-read
version);
4. Availability of a parent or legal guardian to provide information about the
volunteer*s behaviour and symptoms by completing (on-line) questionnaires,
during the institute visit, a separate home-visit or over the telephone,
5. Availability of a parent or carer to accompany the volunteer to all
institute visits where participants are unable to travel on their own;
6. Participant on stable medication (min 8 weeks) at entrance point and over
the course of study.
Typically Developing (TD) control group:
1. Male or female aged 6-30 years;
2. Able to participate and willing to give written informed consent;
For minors <18 years: Informed written consent from the parent or legal
guardian, verbal assent from the volunteer prior to each assessment;
3. For minors <18 years: Availability of a parent who provides information
about behaviour/ symptoms during the institute visit, a separate home-visit or
over the telephone.
Intellectual disabilities (ID) control group:
1. Male or female aged 12-30 years;
2. Presence of syndromic forms of ID (Down*s Syndrome) and/or unspecified
general intellectual disabilities;
3. Availability of a parent or legal guardian to provide written informed
consent; verbal assent from the volunteer prior to each assessment;
4. Availability of parent or caregiver who accompanies the volunteer to all
institute visits and provides information about the volunteer*s behaviour and
symptoms by completing (on-line) questionnaires, and either during the
institute visit, a separate home visit, or over the telephone;
5. Participant on stable medication (minimum 8 weeks) prior to each assessment
visit.
Exclusion criteria
All groups:
1. Presence of significant hearing or visual impairments not correctable by
glasses or hearing aids;
2. A history of alcohol and / or substance abuse or dependence in the past
year;
3. Presence of any MRI counter-indications (e.g., metal implants, braces,
claustrophobia) or failure to give informed written consent to MRI scanning (or
to provide GP details at centres where this is a pre-condition for scanning);
4. Presence or history of any Neurological Disorder/ significant trauma.
ASD group:
Presence of psychosis or bipolar disorder.
TD group:
Presence of any DSM-5 axis I and II psychiatric disorders.
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 | NL72033.091.19 |