Effects of Probiotic Consumption in Children With Autism Spectrum Disorder (ASD)

NCT06568588 | Active Not Recruiting Phase 2

• 1 other identifier: 2023032
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the effects of Saccharomyces boulardii (Sb) consumption on Ecuadorian children with a diagnosis of autism spectrum disorder (ASD) and digestive symptoms. Saccharomyces boulardii is a probiotic, in other words, a beneficial microorganism. The main question it aims to answer is: Does Sb improve intestinal health, defenses against infections, nutrition and behavior of the participants. Researchers will compare children when they are taking and not taking Saccharomyces boulardii to know if there are changes in digestive symptoms, immune system function, nutritional status and behavior. Participants will take Saccharomyces boulardii for 4 months and will be 4 months without taking Sb. All participants must provide stool, urine and blood samples. A medical, nutritional and psychological team will follow the participants at least 5 times during the study.

Conditions

Autism Spectrum Disorder

Keywords

intestinal microbiota; Intestinal metabolome; Autism spectrum disorder; ASD; Nutrition; Immune status; Gastrointestinal symptoms

Outcome Measures

Primary Outcomes (10)

• Modifications of gastrointestinal symptoms during Sb administration

  Changes in gastrointestinal symptoms of children with ASD when they are receiving Sb. Symptoms will be evaluated with Rome IV Pediatric Questionnaire Parent Report For Children and Adolescents Age 4+.

  Gastrointestinal symptoms will be evaluated monthly, through study completion, an average of 1 year

• Modifications of gastrointestinal microbiota during Sb administration

  Changes in alpha diversity, beta diversity, taxonomic composition, functional annotation and differential microbial relative abundance of gastrointestinal microbiota of children with ASD when they are receiving Sb supplementation.

  Fecal samples will be analyzed at months 1, 4, 5, 9 and 10 of the study.

• Modifications of fecal metabolome during Sb administration

  Changes in the fecal metabolome of children with ASD when they are receiving Sb supplementation. Metabolome will be determined with 2D experiments based on signals in H-NMR, using the human metabolome database and the biological magnetic resonance metabolome database.

  Fecal samples will be analyzed at months 1, 4, 5, 9 and 10 of the study.

• Modifications of blood metabolome during Sb administration

  Changes in blood metabolome of children with ASD when they are receiving Sb supplementation. Metabolome will be determined with 2D experiments based on signals in H-NMR, using the human metabolome database and the biological magnetic resonance metabolome database.

  Blood samples will be analyzed at months 1, 4, 5, 9 and 10 of the study.

• Modifications of urine metabolome during Sb administration

  Changes in urine metabolome of children with ASD when they are receiving Sb supplementation. Metabolome will be determined with 2D experiments based on signals in H-NMR, using the human metabolome database and the biological magnetic resonance metabolome database.

  Urine samples will be analyzed at months 1, 4, 5, 9 and 10 of the study.

• Modifications of body mass index (BMI) during Sb administration

  Changes in the BMI of children with ASD when they are receiving Sb supplementation. To obtain BMI, weight (in kilograms) and height (in meters) will be measured.

  BMI will be determined at months 1, 4, 5, 9 and 10 of the study.

• Modifications of nutrient intake during Sb administration

  Changes in the nutrient intake of children with ASD when they are receiving Sb supplementation. The 24-hour reminder questionnaire will be applied to quantify nutrient intake.

  Nutrient intake will be determined at months 1, 4, 5, 9 and 10 of the study.

• Modifications of immune function during Sb administration

  Changes in the immune function of children with ASD when they are receiving Sb supplementation. Levels of interleukins and growth factors will be determined. Specifically, interleukin(IL)-1, IL-4, IL-6, IL-8, tumoral necrosis factor (TNF) -α, interferon (IFN)-γ, IL-10, transforming growth factor (TGF)-β will be measured.

  Blood samples for interleukins and growth factors determination will be analyzed at months 1,4, 5, 9,10 of the study

• Modifications of behavior during Sb administration

  Changes in the behavior of children with ASD when they are receiving Sb supplementation. ADOS- 2 test will be applied to determine conduct in different situations, sensory response and adaptive functioning. The total scores range from 15 to 60, and a higher score means a worse outcome.

  ADOS-2 test will be performed at months 1, 4, 5, 9, 10 of the study.

• Modifications in the intelligence levels during Sb administration

  Changes in the intelligence levels of children with ASD when they are receiving Sb supplementation. Different tests will be used according to the age and language level of the participants. WISC will be used on children from 7 years 4 months of age. WPPSI will be applied to children 7 years 3 months or younger. BATTELLE will be used for children 8 years old or younger who have a low language level. With all of these tests, a higher score means a better outcome.

  Tests will be performed at months 1, 4, 5, 9, 10 of the study.

Study Arms (2)

First four months with Sb (Group A)

EXPERIMENTAL

Children that receive Sb supplements in the initial 4 months of the study.

Drug: S. boulardii CNCM (National Collection of Cultures of Microorganisms) I-745

Last four months with Sb (Group B)

EXPERIMENTAL

Children that receive Sb supplements in the final 4 months of the study.

Drug: S. boulardii CNCM (National Collection of Cultures of Microorganisms) I-745

Interventions

S. boulardii CNCM (National Collection of Cultures of Microorganisms) I-745 DRUG

250 mg three times a day for 4 months

Also known as: Floratil

First four months with Sb (Group A); Last four months with Sb (Group B)

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnostic of Autistic Spectrum Disorders (ASD).
• History of gastrointestinal (GI) disorders, recurrent diarrhea, during the past 6 months.
• Children attending learning or therapy centers or schools.
• Age between 5 and 12 years of age.
• Children whose parents or guardians consent their participation in the study.
• Children who can provide the required biological samples, and their guardians must provide the necessary information to complete the established instruments.
• The parents or guardians of the children must sign the informed consent form in order to be part of the study.

You may not qualify if:

• Use of antibiotics, systemic steroids or antifungal medication during the last 15 days prior to fecal sample collection.
• Acute gastrointestinal, respiratory or febrile processes.
• Severe chronic comorbidities such as cancer, immunosuppression, obstructive respiratory disorders, Crohn's disease, ulcerative colitis, among others, at the discretion of the investigators.
• Probiotics consumption in the last three months prior to study enrollment.
• History of allergy or hypersensitivity to Saccharomyces boulardii or its components, or allergy to yeasts.
• Contraindication and special warning to Saccharomyces boulardii according to the technical Data Sheets, including central venous catheter carriers.

Sponsors & Collaborators

• Universidad San Francisco de Quito: lead
• Biocodex: collaborator
• Neurodesarrollo Quito: collaborator
• University of Illinois at Urbana-Champaign: collaborator

Study Sites (1)

Neurodesarrollo Quito

Quito, Pichincha, Ecuador

Location

Related Publications (4)

• De Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M. Autism spectrum disorders and intestinal microbiota. Gut Microbes. 2015;6(3):207-13. doi: 10.1080/19490976.2015.1035855.

  PMID: 25835343 BACKGROUND

• Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr. 2016 Oct 9;10:91-107. doi: 10.4137/CMPed.S38338. eCollection 2016.

  PMID: 27774001 BACKGROUND

• Zurita MF, Cardenas PA, Sandoval ME, Pena MC, Fornasini M, Flores N, Monaco MH, Berding K, Donovan SM, Kuntz T, Gilbert JA, Baldeon ME. Analysis of gut microbiome, nutrition and immune status in autism spectrum disorder: a case-control study in Ecuador. Gut Microbes. 2020 May 3;11(3):453-464. doi: 10.1080/19490976.2019.1662260. Epub 2019 Sep 18.

  PMID: 31530087 BACKGROUND

• Srikantha P, Mohajeri MH. The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorder. Int J Mol Sci. 2019 Apr 29;20(9):2115. doi: 10.3390/ijms20092115.

  PMID: 31035684 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Paúl A Cárdenas, PhD

  Universidad San Francisco de Quito

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor at the Institute of Microbiology

Model Details: Children diagnosed with ASD will be randomly organized into 2 groups. Group A (n=33) will receive Sb supplements at a dose of 250 mg 3 times a day for a period of 4 months. While Group B (n=33) will not receive supplementation for 4 months. This will be followed by a 30-day "washout" period, during which time neither group consumes probiotics. After this time, the children's groups will change treatment for another four months.

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 23, 2024
• Study Start: January 6, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

EC (1)