Butyrate Supplementation in Children With Autism Spectrum Disorder (ASD) and Functional Gastrointestinal Disorders

NCT06514573 | Recruiting DMC

• 1 other identifier: RF-2021-12374286
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 3

Brief Summary

Autism spectrum disorder (ASD) is a neurodevelopmental condition occurring in 1:77 Italian children. Several comorbidities are reported, including functional gastrointestinal disorders (FGIDs) present in up to 70% of patients. FGIDs are disorders resulting from a combination of symptoms affecting motility, hypersensitivity, and other functions, which are not caused by anatomic or organic origin and that impact the severity of ASD core symptoms and complicate the clinical management of ASD children, especially those who are non-verbal. Evidence reports gut microbiome (GM) remodelling in ASD children, and postbiotic butyrate, a GM-derived metabolite, attenuates FGIDs in children and restores social behavior in ASD mouse models. Clinical data on butyrate effects in ASD are still scanty. The present study investigates the therapeutic effects of a 16-week oral postbiotic supplementation on clinical/behavioral profiles, gastrointestinal disturbances, gut microbiome, and immune and inflammatory biomarkers in peripheral blood and fecal samples in children with ASD and FGIDs. Using the Machine Learning (ML) approach, a subset of artificial intelligence, this study also aims to identify predictive factors implicated in the effect of the postbiotic supplementation on FGIDs, important for prevention through modulation of the microbiota. The investigators expect that treating FGIDs will have an impact on the behavioral and core symptoms of ASD and the quality of life of children and their families.

Conditions

Autism Spectrum Disorder (ASD)

Keywords

Autism Spectrum Disorder; Child; Gastrointestinal Microbiome; Microbiota; Butyrates; Fatty Acids, Volatile; Gastrointestinal Diseases; Behavioral symptoms; Gastrointestinal Symptoms; Signs and Symptoms, Digestive; Inflammatory Profile; Functional Gastrointestinal Disorders

Outcome Measures

Primary Outcomes (1)

• Gastrointestinal symptom severity.

  Rate of subjects presenting a clinically relevant improvement in Functional Gastrointestinal Disorders (FGIDs) severity, measured by 6-item Gastrointestinal Severity Index (6-GSI) score decrease \>4 points. The Gastrointestinal Severity Index (6-GSI) score is the sum of the individual item scores. The higher it is, the worse is the outcome. Score range for each item: 0, 1, 2 (0 no symptoms, 1 mild symptoms, 2 severe symptoms).

  At baseline (Timepoint 0) and at 4 months (Timepoint 1)

Secondary Outcomes (20)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  At 4 months (Timepoint 1) and at 8 months (Timepoint 2)

• Unexplained daytime irritability

  At 4 months (Timepoint 1) and at 8 months (Timepoint 2)

• Nocturnal awakening

  At 4 months (Timepoint 1) and at 8 months (Timepoint 2)

• Persistency of Functional Gastrointestinal Disorders severity improvement

  At 4 months (Timepoint 1) and at 8 months (Timepoint 2)

• Gut Microbiota structure and function (fecal Short-Chain Fatty Acids levels, SCFAs)

  At baseline (Timepoint 0) and at 4 months (Timepoint 1)

Study Arms (2)

Butyrate

EXPERIMENTAL

The butyrate groups (butyrate \<=20 kg, butyrate \>20 kg) will receive oral sodium butyrate (dose of 20 mg/kg body weight/daily in sachets, up to 800 mg/day maximum dose) plus ASD standard care.

Dietary Supplement: Sodium Butyrate

Placebo

PLACEBO COMPARATOR

The placebo groups (placebo \<=20 kg, placebo \>20 kg) will receive placebo (cornstarch) at the same dose and time plus ASD standard care.

Dietary Supplement: Placebo (cornstarch)

Interventions

Sodium Butyrate DIETARY_SUPPLEMENT

Daily supplementation with 1 sachet per day for 16 weeks

Butyrate

Placebo (cornstarch) DIETARY_SUPPLEMENT

Daily supplementation with 1 sachet per day for 16 weeks

Placebo

Eligibility Criteria

• Age: 3 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• children aged 3-6 years
• both sexes
• ASD diagnosis and presence of FGIDs (6-item Gastrointestinal Severity Index (6-GSI) \>7 from \> 3 months)

You may not qualify if:

• age 6 years
• uncertain FGIDs diagnoses
• FGIDs symptoms duration \<3 months
• concomitant presence of other chronic condition (adverse food reactions, metabolic disorders, infections)
• malformation and Gi or urinary tracts chronic diseases
• immunodeficiencies
• diabetes
• neurologic/cardiovascular/autoimmune diseases
• obesity
• malnutrition
• antibiotics and/or pre-/pro-/synbiotics use 6 months prior to enrollment
• last 12 months participation into other clinical trials

Sponsors & Collaborators

• Istituto Superiore di Sanità: lead
• University of Rome Tor Vergata: collaborator
• Federico II University: collaborator

Study Sites (3)

Azienda Ospedaliera Universitaria Federico II

Naples, 80131, Italy

RECRUITING

Policlinico Tor Vergata Hospital

Rome, 00133, Italy

RECRUITING

Istituto Superiore di Sanità

Rome, 00161, Italy

RECRUITING

Related Publications (18)

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• Coretti L, Paparo L, Riccio MP, Amato F, Cuomo M, Natale A, Borrelli L, Corrado G, Comegna M, Buommino E, Castaldo G, Bravaccio C, Chiariotti L, Berni Canani R, Lembo F. Gut Microbiota Features in Young Children With Autism Spectrum Disorders. Front Microbiol. 2018 Dec 19;9:3146. doi: 10.3389/fmicb.2018.03146. eCollection 2018.

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• Liu J, Gao Z, Liu C, Liu T, Gao J, Cai Y, Fan X. Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder. Front Cell Dev Biol. 2022 Mar 3;10:792490. doi: 10.3389/fcell.2022.792490. eCollection 2022.

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• Wei L, Singh R, Ro S, Ghoshal UC. Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology. JGH Open. 2021 Mar 23;5(9):976-987. doi: 10.1002/jgh3.12528. eCollection 2021 Sep.

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• Turriziani L, Ricciardello A, Cucinotta F, Bellomo F, Turturo G, Boncoddo M, Mirabelli S, Scattoni ML, Rossi M, Persico AM. Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study. Autism Res. 2022 Jan;15(1):56-69. doi: 10.1002/aur.2639. Epub 2021 Nov 23.

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MeSH Terms

Conditions

Autism Spectrum Disorder; Gastrointestinal Diseases; Behavioral Symptoms; Signs and Symptoms, Digestive

Interventions

Butyric Acid; Starch

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Digestive System Diseases; Behavior; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• Maria Luisa Scattoni, Ph.D.

  Istituto Superiore di Sanità

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Luisa Scattoni, Ph.D.

CONTACT

+39 0649903104; marialuisa.scattoni@iss.it

Maria Puopolo, MSc

CONTACT

+39 0649903087; maria.puopolo@iss.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding will be maintained by making the capsules look identical. Both participants and the research staff who collect the outcome data will be blinded to treatment status. All the data will be recorded anonymously and entered into the study database by each researcher. A blinded statistician will analyze the data.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind randomized, parallel-group, placebo-controlled study. Groups will receive oral sodium butyrate or placebo (cornstarch) for 16 weeks. The sachets and content of treatments will be indistinguishable (same color, smell, taste) and prepared by the Central Pharmacy Service of the Academic Hospital Federico II of Naples. Parents will receive an anonymous white paper box containing the sachets of placebo or butyrate, instructions for storing at room temperature, preparation (mixing the powder in water, milk, or foods), the daily amount of product, and maintaining the habitual child diet, avoiding probiotics, prebiotics, synbiotics during the entire study.

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 23, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)