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

NCT05796310 | Unknown

• 1 other identifier: SPECTRUM01
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autism Spectrum Disorder

Keywords

Autism, miRNA, Eye Tracker, biomarkers

Outcome Measures

Primary Outcomes (4)

• Salivary miRNA profile

  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

  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

  Total fixation duration measurements in pre-selected areas (areas of interest)

  At time of enrollment

• eye-gaze path characteristics - pupillary response

  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 Outcomes (3)

• Autism Diagnostic Observation Schedule 2 (ASD patients only)

  At time of enrollment

• Vineland Adaptive Behavior Scales (VABS) II (ASD patients only)

  At time of enrollment

• Intellectual Quotient (ASD patients only)

  At time of enrollment

Study Arms (3)

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; Diagnostic Test: eye-tracking recorder; Diagnostic Test: neuropsychological assessment

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; Diagnostic Test: eye-tracking recorder

Typical Development children

This group is comprised of 3-17 years children with typical development.

Diagnostic Test: Salivary collection; Diagnostic Test: eye-tracking recorder

Interventions

Salivary collection DIAGNOSTIC_TEST

Collection of saliva via swab for miRNA processing

Autism Spectrum Disorder Patients; Siblings of children with Autism Spectrum Disorders; Typical Development children

eye-tracking recorder DIAGNOSTIC_TEST

Administration of eye-tracking session recording Saccadic Eye Movements, fixation duration and pupillary response.

Autism Spectrum Disorder Patients; Siblings of children with Autism Spectrum Disorders; Typical Development children

neuropsychological assessment DIAGNOSTIC_TEST

Administration of neuropsychological tests and collected patient medical history

Autism Spectrum Disorder Patients

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Age Groups: Child (0-17)
• 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).

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.).
• 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.

Sponsors & Collaborators

• IRCCS Centro Neurolesi Bonino Pulejo: lead
• Regione Sicilia: collaborator

Study Sites (1)

IRCCS Centro Neurolesi Bonino Pulejo

Messina, 98100, Italy

RECRUITING

Related Publications (15)

• Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM. Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders. Mol Autism. 2015 Jun 19;6:37. doi: 10.1186/s13229-015-0029-9. eCollection 2015.

  PMID: 26146533 BACKGROUND

• Frazier TW, Coury DL, Sohl K, Wagner KE, Uhlig R, Hicks SD, Middleton FA. Evidence-based use of scalable biomarkers to increase diagnostic efficiency and decrease the lifetime costs of autism. Autism Res. 2021 Jun;14(6):1271-1283. doi: 10.1002/aur.2498. Epub 2021 Mar 8.

  PMID: 33682319 BACKGROUND

• Frazier TW, Klingemier EW, Parikh S, Speer L, Strauss MS, Eng C, Hardan AY, Youngstrom EA. Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):858-866. doi: 10.1016/j.jaac.2018.06.023. Epub 2018 Sep 13.

  PMID: 30392627 BACKGROUND

• Frazier TW, Strauss M, Klingemier EW, Zetzer EE, Hardan AY, Eng C, Youngstrom EA. A Meta-Analysis of Gaze Differences to Social and Nonsocial Information Between Individuals With and Without Autism. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):546-555. doi: 10.1016/j.jaac.2017.05.005. Epub 2017 May 11.

  PMID: 28647006 BACKGROUND

• Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.

  PMID: 17404130 BACKGROUND

• Ghahramani Seno MM, Hu P, Gwadry FG, Pinto D, Marshall CR, Casallo G, Scherer SW. Gene and miRNA expression profiles in autism spectrum disorders. Brain Res. 2011 Mar 22;1380:85-97. doi: 10.1016/j.brainres.2010.09.046. Epub 2010 Sep 21.

  PMID: 20868653 BACKGROUND

• Hicks SD, Ignacio C, Gentile K, Middleton FA. Salivary miRNA profiles identify children with autism spectrum disorder, correlate with adaptive behavior, and implicate ASD candidate genes involved in neurodevelopment. BMC Pediatr. 2016 Apr 22;16:52. doi: 10.1186/s12887-016-0586-x.

  PMID: 27105825 BACKGROUND

• Hicks SD, Rajan AT, Wagner KE, Barns S, Carpenter RL, Middleton FA. Validation of a Salivary RNA Test for Childhood Autism Spectrum Disorder. Front Genet. 2018 Nov 9;9:534. doi: 10.3389/fgene.2018.00534. eCollection 2018.

  PMID: 30473705 BACKGROUND

• Leblond CS, Le TL, Malesys S, Cliquet F, Tabet AC, Delorme R, Rolland T, Bourgeron T. Operative list of genes associated with autism and neurodevelopmental disorders based on database review. Mol Cell Neurosci. 2021 Jun;113:103623. doi: 10.1016/j.mcn.2021.103623. Epub 2021 Apr 29.

  PMID: 33932580 BACKGROUND

• Mor M, Nardone S, Sams DS, Elliott E. Hypomethylation of miR-142 promoter and upregulation of microRNAs that target the oxytocin receptor gene in the autism prefrontal cortex. Mol Autism. 2015 Aug 14;6:46. doi: 10.1186/s13229-015-0040-1. eCollection 2015.

  PMID: 26273428 BACKGROUND

• Narzisi A, Costanza C, Umberto B, Filippo M. Non-pharmacological treatments in autism spectrum disorders: an overview on early interventions for pre-schoolers. Curr Clin Pharmacol. 2014 Feb;9(1):17-26. doi: 10.2174/15748847113086660071.

  PMID: 24050743 BACKGROUND

• Narzisi A, Posada M, Barbieri F, Chericoni N, Ciuffolini D, Pinzino M, Romano R, Scattoni ML, Tancredi R, Calderoni S, Muratori F. Prevalence of Autism Spectrum Disorder in a large Italian catchment area: a school-based population study within the ASDEU project. Epidemiol Psychiatr Sci. 2018 Sep 6;29:e5. doi: 10.1017/S2045796018000483.

  PMID: 30187843 BACKGROUND

• Palomo R, Belinchon M, Ozonoff S. Autism and family home movies: a comprehensive review. J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S59-68. doi: 10.1097/00004703-200604002-00003.

  PMID: 16685187 BACKGROUND

• Sarachana T, Zhou R, Chen G, Manji HK, Hu VW. Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines. Genome Med. 2010 Apr 7;2(4):23. doi: 10.1186/gm144.

  PMID: 20374639 BACKGROUND

• Zwaigenbaum L, Bryson S, Garon N. Early identification of autism spectrum disorders. Behav Brain Res. 2013 Aug 15;251:133-46. doi: 10.1016/j.bbr.2013.04.004. Epub 2013 Apr 12.

  PMID: 23588272 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Salivary RNA

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Central Study Contacts

Francesca Cucinotta, MD, PhD

CONTACT

09060128256; francesca.cucinotta@irccsme.it

IRCCS Centro Neurolesi Bonino Pulejo Bio-parco delle intelligenze e delle neuro-fragilità

CONTACT

info@irccsme.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: April 3, 2023
• Study Start: July 28, 2022
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: April 3, 2023

Record last verified: 2023-03

Locations

IT (1)