Intestinal Dysbiosis and BBB Integrity in Autism

NCT04321915 | Recruiting

• 1 other identifier: RECHMPL18_0197
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Autism Spectrum Disorder (ASD) is characterised by an impairment of social interactions and communication, associated with repetitive behaviour and restrictive interests. Clinical phenotypes of this neurodevelopmental disorder are heterogeneous and surprisingly up to 70% of ASD patients have gastro-intestinal (GI) disorders, associated with ASD severity and influence by feeding disorders. Gut-brain axis seems to play a key role in neurodevelopment and ASD pathophysiology. Indeed an intestinal dysbiosis is observed in ASD, as well as intestinal inflammation and permeability. Aspecific inflammatory pattern suggests neuroinflammation processes in ASD. Neuroinflammation is involved in blood brain barrier (BBB) integrity and there are some arguments for a putative BBBimpairment in ASD. Nevertheless, no study has explored all together these parameters in ASD patients. Here we hypothesise that intestinal dysbiosis in ASD could lead to a BBB impairment through neuroinflammation processes. Furthermore, this association between intestinal dysbiosis and BBB impairment could be influenced by a lot of clinical characteristics, such as ASD severity or GI disorders presence. The principal aim of our study is to determine if the gut microbiota composition is associated with the BBB integrity in ASD. The secondary objectives are i) too identify in children with ASD some physiopathological pathways involved in this association, with a focus on associations betweenintestinal dysbiosis, intestinal permeability, intestinal permeability, the Th1/Th2 immune response, neuroinflammation and the BBB integrity; ii) to evaluate the influence of these associations on several clinical features of ASD such as ASD severity or GI disorders intensity; iii) to evaluate the influence of nutritional status on biological and clinical parameters. This study will assess a lot of clinical and biological parameters together, some of them were never explored in ASD children. It will allow to better understand ASD pathophysiology, to highlight new therapeutic pathway, and to promote personalised medicine.

Conditions

Autism Spectrum Disorder

Keywords

intestinal microbiota; neuroinflammation; brain blood barrier; autism spectrum disorders

Outcome Measures

Primary Outcomes (1)

• Intestinal microbiota assessment

  At the end of the study, the analysis will be performed on all the samples at the same time by 16S RNAr pyrosequencing.

  9 months

Secondary Outcomes (16)

• Measuring the severity of ASD

  24 months

• Evaluation of the level of social interaction

  24 months

• Behavioural disorders

  24 months

• Quality of life of children with ASD

  24 months

• Developmental trajectory of children with ASD

  24 months

Study Arms (1)

Children with Autism spectrum disorder

OTHER

Patients will realised quesstionnaires, a blood sample will be collected, the feces will be collected too. The analysis of intestinal microbiota and neuroinflammation markers will be processed.

Other: Analysis of intestinal microbiota in autism spectrum desorder; Other: Analysis of neuroinflammation markers in autism spectrum desorder

Interventions

Analysis of intestinal microbiota in autism spectrum desorder OTHER

This analysis permit to describe the diversity and composition of microbiota and the factors that may influence them. In fact, the gut microbiota plays a key role in regulating the gut-brain axis

Children with Autism spectrum disorder

Analysis of neuroinflammation markers in autism spectrum desorder OTHER

This analysis permit to reveal the integrity of the blood-brain barrier (BBB) which is affected in autism spectrum desorder.

Children with Autism spectrum disorder

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Child from the ELENA cohort who received at least 3 years of follow-up in this cohort and a diagnosis of ASD
• Aged 6 to 16 years
• Living in Languedoc-Roussillon
• Consent to participate in the study signed by the legal representative

You may not qualify if:

• Syndromic autism (neuroanatomical abnormality detected on brain MRI, severe neurological syndrome or polymalformative)
• Known severe gastrointestinal pathology (such as celiac disease or Crohn's disease)
• Other known severe chronic disease (e.g., diabetes)
• Specific diet (gluten-free, casein-free, ketogenic, protein-enriched) within 6 months
• ADOS Level Module 4 (due to the impossibility of calculating a ADOS-CSS score in this case)
• Not affiliated to a French social security scheme or not beneficiaries of such a scheme
• Refusal of blood test
• Pregnant women

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• LBPC, Inserm 1183, IRMB CHU Montpellier: collaborator
• UMR 5203, InsermU1191, IGF, Montpellier: collaborator

Study Sites (1)

Centre de Ressources Autisme

Montpellier, 34295, France

RECRUITING

MeSH Terms

Conditions

Autism Spectrum Disorder; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stéphanie MIOT, MD-PH

  Montpellier University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stéphanie MIOT, MD-PhD

CONTACT

467339687; s-miot@chu-montpellier.fr

Amaria BAGHDADLI, PU-PH

CONTACT

467336383; a-baghadadli@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2020
• First Posted: March 25, 2020
• Study Start: April 26, 2021
• Primary Completion: December 26, 2024
• Study Completion: February 26, 2025
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

FR (1)