Combination of Predictive Biomarkers to Increase Diagnostics Efficiency of Autism Spectrum Disorder

March 30, 2023 updated by: Francesca Cucinotta, IRCCS Centro Neurolesi "Bonino-Pulejo"

Mind the Gap: a Bridge Between Research and Clinic for the Prevention and Diagnosis of Autism Spectrum Disorders

Early identification and diagnosis of autism spectrum disorder (ASD) is necessary to promote access to early treatment. Despite the high incidence, in Italy it is estimated that 1 in 77 children (age 7-9 years) (Narzisi et al., 2018), the diagnosis and the choice of rehabilitation treatment for patients with Autism Spectrum Disorder (ASD) are still based on clinical observation. In the absence of targeted pharmacological therapies, early surveillance and evaluation aimed at timely intervention represent the only successful strategy to reduce the severity of symptoms (Palomo R et al., 2006) and improve the quality of life of children affected by ASD and their families, thus also leading to a reduction in costs for the National Health Service (Ganz ML. 2007). However, compared to the great advances in neuroscience, the clinical management of autistic individuals is seriously lagging behind, and the disorder is often diagnosed after 3-4 years of age despite the presence of deficits starting from the very first months of life (Zwaigenbaum L et al. al., 2013). The aim of this project is to bridge the gap between research and clinic, thanks to the convergence of multiple biological and clinical data.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purpose of this project is to combine multiple biological levels of information and their matching with the clinical phenotype and personal/family anamnesis of the single individual. In fact, by stratifying multiple levels of biomarkers, including behavioral (eye tracking), clinical and neuropsychological variables, parameters taken from transcriptomics (RNAseq), the goal is to identify a panel of intermediate biomarkers capable of (a) distinguishing autistic subjects from typically developing brothers/sisters, (b) to distinguish autistic subjects from typically developing subjects, (c) to stratify autistic patients into a limited number of homogeneous subgroups by physiopathology, in order to allow personalized pharmacology and improve their management clinic.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: IRCCS Centro Neurolesi Bonino Pulejo Bio-parco delle intelligenze e delle neuro-fragilità
  • Email: info@irccsme.it

Study Locations

  • Italy
      • Messina, Italy, 98100
        • Recruiting
        • Irccs Centro Neurolesi Bonino Pulejo
        • Contact:
          • IRCCS Centro Neurolesi Bonino Pulejo Bio-parco delle intelligenze e delle neuro-fragilità
          • Phone Number: 09060128256
          • Email: info@irccsme.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years to 17 years (Child)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with the following characteristics will be recruited:

  1. a cohort of at least 25 outpatients with Autism Spectrum Disorder (diagnosed According to Diagnostic and Statistical Manual of Mental Disorders 5 criteria), aged between 4 and 17 years;
  2. a cohort of at least 25 healthy sibs of enrolled autistic patients, aged 4 to 17 years;
  3. a cohort of a minimum of 25 healthy controls, aged between 4 and 17 years, matched by sex and age to the ASD patients recruited (+/- 3 years).

Description

Autistic Spectrum Disorder patients, Inclusion Criteria:

  • aged between 4 and 17years;
  • Autism Spectrum Disorder diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria;
  • healthy brothers/sisters, aged 4 to 17 years;
  • adequate ocular vision, i.e. absence of objective eye problems such as double vision, cataracts, etc.;
  • ability to maintain position in front of the monitor, i.e. knowing how to maintain or regain posture independently or with the help of postural aids;
  • cognitive skills appropriate to the task such as being able to recognize images.

ASD siblings and Typical Developmental children, Inclusion Criteria

  • aged between 4 and 17years;
  • typical development, absence of known pathologies;
  • adequate ocular vision, i.e. absence of objective eye problems such as double vision, cataracts, etc.;
  • ability to maintain position in front of the monitor, i.e. knowing how to maintain or regain posture independently or with the help of postural aids;
  • cognitive skills appropriate to the task such as being able to recognize images.

Autistic Spectrum Disorder patients, Exclusion Criteria:

  • age not between 4 years and 17 years;
  • difficulty in controlling ocular motility and visual hookup;
  • unavailability of at least one sibling to participate in the diagnostic process;
  • subjects with a syndromic phenotype or for which the presence of a known genetic syndrome has already been ascertained (e.g. Syndrome Rett, Xfra, Tuberous Sclerosis, etc.).

ASD siblings and Typical Developmental children, Exclusion Criteria:

  • age not between 4 years and 17 years;
  • subjects diagnosed with moderate/severe intellectual disability, or affected by known neurological pathologies (infantile cerebral palsy, epilepsy, sensory deficits) or with a history of preterm birth (≤32w) or underweight (≤10°ile for gestational age);
  • subjects with a syndromic phenotype or for which the presence of a known genetic syndrome has already been ascertained (e.g. Syndrome Rett, Xfra, Tuberous Sclerosis, etc.);
  • difficulty in controlling ocular motility and visual hookup;
  • subjects suffering from neurodevelopmental disorders or family history for ASD for the control group.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Autism Spectrum Disorder Patients
This group is comprised of 3-17 years children with an expert clinical diagnosis of autism spectrum disorders.
Diagnostic test: Salivary collection
Collection of saliva via swab for miRNA processing
Diagnostic test: eye-tracking recorder
Administration of eye-tracking session recording Saccadic Eye Movements, fixation duration and pupillary response.
Diagnostic test: neuropsychological assessment
Administration of neuropsychological tests and collected patient medical history
Siblings of children with Autism Spectrum Disorders
This group is comprised of 3-17 years old siblings, with typical development, of a child with an expert clinical diagnosis of autism spectrum disorders.
Diagnostic test: Salivary collection
Collection of saliva via swab for miRNA processing
Diagnostic test: eye-tracking recorder
Administration of eye-tracking session recording Saccadic Eye Movements, fixation duration and pupillary response.
Typical Development children
This group is comprised of 3-17 years children with typical development.
Diagnostic test: Salivary collection
Collection of saliva via swab for miRNA processing
Diagnostic test: eye-tracking recorder
Administration of eye-tracking session recording Saccadic Eye Movements, fixation duration and pupillary response.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Salivary miRNA profile
Time Frame: At time of enrollment
Measures of salivary miRNA profile - identify the microRNAs differentially expressed in patients with autism spectrum disorder compared to sibling and healthy controls.
At time of enrollment
eye-gaze path characteristics - Saccadic Eye Movements
Time Frame: At time of enrollment
Saccadic eye movement assessments measure the speed and accuracy of a participant's saccadic eye movements in response to various stimuli.
At time of enrollment
eye-gaze path characteristics - fixation time
Time Frame: At time of enrollment
Total fixation duration measurements in pre-selected areas (areas of interest)
At time of enrollment
eye-gaze path characteristics - pupillary response
Time Frame: At time of enrollment
pupillary response measurements assess the changes of mean pupil diameters for the left and right eyes after exposition to pre-selected immages (areas of interest)
At time of enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Autism Diagnostic Observation Schedule 2 (ASD patients only)
Time Frame: At time of enrollment
Ados2 is a semi-structured, standardised assessment to measure autistic behaviors.
At time of enrollment
Vineland Adaptive Behavior Scales (VABS) II (ASD patients only)
Time Frame: At time of enrollment
The VABS II is a standardized semi-structured interview to measure adaptive behavior.
At time of enrollment
Intellectual Quotient (ASD patients only)
Time Frame: At time of enrollment
Intellectual quotient measured using one cognitive test per subject, chosen depending on age and language development (either Griffiths Developmental Rating Scales, Wechsler Intelligence Scale for Children - Fourth Edition, or Leiter III).
At time of enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS Centro Neurolesi "Bonino-Pulejo"

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Regione Sicilia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 28, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 3, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPECTRUM01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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