Intestinal Permeability in Children With Autism Spectrum Disorder

NCT ID: NCT07032857

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 55 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-09-30

Brief Summary

In recent years, increasing attention has been directed toward the role of the gut-brain axis in the pathogenesis of neurodevelopmental disorders, particularly Autism Spectrum Disorder (ASD). Among the multiple contributing factors, the integrity of the intestinal barrier appears to play a crucial role. Enhanced paracellular permeability ("leaky gut") may allow luminal antigens and microbial metabolites to translocate into the systemic circulation, triggering inflammatory responses that could impact neuropsychological functioning.

Several studies suggest that, although intestinal permeability is not universally altered in all individuals with ASD, there exists a subset characterized by selective epithelial dysfunction, especially associated with repetitive and stereotyped behaviors.

This project aims to investigate, through a controlled sibling-based design, whether intestinal permeability indices are significantly altered in children with ASD and whether such alterations are specifically correlated with behavioral domains assessed through the ADOS instrument.

Detailed Description

Study Objectives

Primary Objective:

• To compare intestinal permeability profiles in children with ASD and their neurotypical siblings, using the La/Ma ratio and the recovery of specific sugars (lactulose, mannitol, sucrose, sucralose).

Secondary Objectives:

• To explore the correlations between intestinal permeability markers and behavioral dimensions assessed via ADOS, with particular focus on stereotyped behaviors and communication.
• To assess the presence of intestinal inflammation through fecal calprotectin (FC) measurement.

Study Design Observational, case-control, single-center clinical study involving children with ASD and unaffected siblings. The intra-family design allows for control of shared environmental and genetic factors.

Study Population

ASD Group (cases):

• Children with a clinical diagnosis of ASD according to DSM-IV, confirmed by ADOS-G.
• Aged between 2 and 14 years.

Control Group (siblings):

• Unaffected siblings who underwent expert clinical evaluation to exclude neurodevelopmental disorders.
• SCQ score below the risk threshold for ASD.

Experimental Methodology 7.1 Intestinal Permeability Test (IPT)

• Fasting and abstention from NSAIDs/alcohol for at least 72 hours.
• Baseline urine sample collection.
• Oral administration of a sugar cocktail containing:

• Lactulose 5 g
• Mannitol 1 g
• Sucrose 20 g
• Sucralose 1 g
• Collection of all urine passed during the following 6 hours.
• Samples stored at -80°C with sodium azide.

Biochemical Analyses

• Sugar quantification via UPLC-MS/MS (Waters ACQUITY™).
• Use of isotopically labeled internal standards and seven-point calibration curves.
• Calculation of urinary recovery percentages and La/Ma ratio.
• FC measured via ELISA (Calprest®). Behavioral Assessment Tools
• ADOS-G: severity assessment in communication, social interaction, and stereotyped behavior domains.
• SCQ: ASD screening in controls.
• IQ assessed with standardized psychometric tests.

Statistical Analysis

• Descriptive statistics using mean ± SD or median (IQR).
• Shapiro-Wilk test for normality.
• Welch's t-test or Mann-Whitney U test for group comparisons.
• Fisher's exact test for categorical variables.
• Spearman's rank correlation (ρ) for associations between permeability indices and behavioral variables.

Relevance and Future Perspectives This protocol contributes to the growing body of translational research exploring the impact of intestinal function on neurodevelopmental disorders. The potential to identify biomarkers associated with specific behavioral domains may inform future personalized therapeutic strategies, including those targeting the intestinal barrier through prebiotics, probiotics, or anti-inflammatory nutraceuticals.

Conditions

Autism Spectrum Disorders

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Autism spectrum disorders

Intestinal Permeability Assessment

No interventions assigned to this group

Sibilings

Intestinal Permenability Assessmnt

No interventions assigned to this group

Eligibility Criteria

Exclusion Criteria

• Known neurological disorders.
• Major congenital anomalies.
• Severe head trauma.
• Chronic gastrointestinal diseases.
• Special diets (e.g., gluten-free or gluten/casein-free).
• Antibiotic or probiotic/prebiotic intake in the previous 4 weeks.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bari

OTHER

Sponsor Role: lead

Responsible Party

Ruggiero Francavilla

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Of Bari Aldo Moro

Bari, BA, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Ruggiero Francavilla, Prof

Role: CONTACT

rfrancavilla@gmail.com

00390805592063

fernanda Cristofori, MD

Role: CONTACT

fernandacristofori@gmail.com

00393384176598

Facility Contacts

Ruggiero Francavilla, Prof

Role: primary

rfrancavilla@gmail.com

00390805592063

Fernanda Cristofori, MD

Role: backup

fernandacristofori@gmail.com

3384176598

Other Identifiers

IP-ASD

Identifier Type: -

Identifier Source: org_study_id