Assessing the Impact of Probiotic Supplementation in Children Diagnosed with Autism Spectrum Disorder: the PROBI-O-TISM Study ((PROBI-O-TISM))

Children with autism spectrum disorder (ASD) present with stereotyped behaviors and often with comorbidities including gastrointestinal symptoms and sleep disturbances. These affect the quality of life of both children and parents. As of now, interventions available to manage ASD-related behaviors rely heavily on the services of professionals who are often difficult to access. What is even more striking is that there are currently no approved medications to treat the core symptoms of ASD. There is an important need for additional strategies to manage severity of ASD and to develop new treatments.

Targeting the bacteria living in the intestine, named 'gut microbiota', by using probiotics is an avenue that has been proposed by other groups to improve behaviors associated with ASD and gastrointestinal symptoms. However, these studies have important limitations, pressing the need for robustly designed interventions.

Previously, the PROBI-O-TISM pilot study was conducted at CHU Sainte-Justine. The investigators confirmed that the Bio-K+ probiotic beverage is acceptable and safe for autistic children and that the proposed study protocol is feasible. The study also led to promising preliminary results suggesting a beneficial effect of the probiotics on behaviors, gastrointestinal symptoms and sleep.

The proposed study will answer the question: ''Does supplementing with Bio-K+ probiotics reduce the severity of autistic behaviors and comorbidities in children with a diagnosis of ASD? '' The investigators will use a solid study design, a double-blinded randomized controlled-trial with placebo, to test the efficacy of a 14-week treatment with daily Bio-K+ probiotic supplement in children aged 4 to 11 years old. The investigators will also study the impact of the supplementation on other parameters such as quality of life, gut microbiota and brain signaling.

This is a unique opportunity to test a simple approach to improve behaviors and comorbidities in autistic children.

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Dietary supplement: Three strains of Lactobacillus: L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Valérie Marcil, Professor; Phone Number: 3272 514 345-4931; Email: valerie.marcil@umontreal.ca
• Study Contact Backup: Name: Ghizlane Gaougaou, Research associate; Phone Number: 5745 514 345-4931; Email: ghizlane.gaougaou@umontreal.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
      • Contact: Valérie Marcil, Professor; Phone Number: 3272 514-345-4931; Email: valerie.marcil@umontreal.ca
      • Contact: Ghizlane Gaougaou, Research Associate; Phone Number: 5745 514-345-4931; Email: ghizlane.gaougaou@umontreal.ca
      • Contact: Valérie Marcil, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Being an autistic child with normal intelligence as documented by a neuropsychology assessment at the time of ASD diagnosis based on the ADOS score and the clinical impression of a multidisciplinary team of experts in autism diagnosis in the Department of Psychiatry;
• Being between the ages of 4 and 11 years;
• Acceptance and ability of the child to consume the probiotics product.

Exclusion Criteria:

• Epilepsy;
• Autism in the context of a genetic syndrome such as Fragile X or Bourneville sclerosis;
• Known presence of cancer, diabetes, celiac disease or inflammatory bowel disease (Crohn's disease or ulcerative colitis);
• Genetic disorder such as trisomy 21 or 14;
• Immune system disorder;
• Intolerance or allergy to Bio-K+ pea-based probiotics;
• Having taken antibiotics or probiotics in the previous 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; A fermented probiotic beverage containing 3 lactobacilli	Dietary supplement: Three strains of Lactobacillus: L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; A probiotic beverage (98 g) at dose of 50.10^9 CFU, taken once daily for 14 weeks.
Placebo Comparator: Placebo; A beverage without bacteria (identical taste and nutritional content to the probiotic beverage)	Other: Placebo; Non fermented beverage (98 g) with no probiotic strains, taken once daily for 14 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in ATEC (Autism Treatment Evaluation Checklist) total score between baseline and week 14	Mean change in ATEC total score between baseline and week 14 will be compared to verify the supplementation effects. ATEC scale consists of 77 items grouped into four subscales: (1) language, (2) perception, (3) sociability and (4) behavior. The total score is 0-179; the higher the score, the more severe ASD-related behaviors	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in ATEC (Autism Treatment Evaluation Checklist) total score between week 14 and week 18	Mean change in ATEC total score between week 14 and week 18 will be compared to verify persistence of treatment effects after wash-out (product cessation). The total score is 0-179; the higher the score, the more severe ASD-related behaviors.	4 weeks
Mean change in each ATEC (Autism Treatment Evaluation Checklist) sub-scores (language, perception, sociability, and behavior) between baseline , week 14 and week 18 .	Mean change in each ATEC sub-scores (language, perception, sociability, and behavior) will be compared between baseline, week 14 to verify supplementation effect and week 18 to evaluate persistence of treatment effects after wash-out (product cessation). The total score is 0-179; the higher the score, the more severe ASD-related behaviors.	Baseline, 14 weeks and 18 weeks
Mean change in ATEC (Autism Treatment Evaluation Checklist) total score at week 4 and week 8 from baseline.	Mean change in ATEC total score at week 4 and from baseline will be collected to document effect over time. The total score is 0-179; the higher the score, the more severe ASD-related behaviors	4 weeks and 8 weeks
Mean change in VABS-III (adaptive behavior skills) total and sub-scores between baseline, week 14 and week 18.	Mean change in VABS-III total and sub-scores will be compared between baseline, week 14 to determine supplementation effect and week 18 to verify persistence of treatment effects after wash-out (product cessation). It consists of four subscales: communication, daily living skills, socialization and motor skills. The total score (range 0-72) and the four sub-scores total will be calculated. The higher scores indicate higher levels of functioning.	Baseline, 14 weeks and 18 weeks
Mean change in 6-GSI (6-Gastrointestinal Severity Index) score between baseline, week 4, week 8, week 14 and week 18.	Mean change in 6-GSI score will be compared between baseline, week 4, week 8, week 14 to evaluate supplémentation effect and week 18 to verify to persistence of treatment effects after wash-out (product cessation).The total score is 0-12, with higher values indicating greater severity.	From baseline up to 18 weeks.
Mean change in CSHQ (Child's Sleep Habits Questionnaire) total and sub-scores between baseline, week 4, week 8, week 14 and week 18.	Mean change in CSHQ total and sub-scores will be compared between baseline, week 4, week 8, week 14 to evaluate suplementation effects and week 18 to verify persistence of treatment effects after wash-out (product cessation). Total score is 33-99 divided in eight subscales: (1) bedtime resistance, (2) sleep-onset delay, (3) sleep duration, (4) sleep anxiety, (5) nocturnal awakenings, (6) parasomnias, (7) sleep disordered breathing and (8) morning waking/daytime sleepiness. The higher the CSHQ score the greater the complaints.	From baseline up to 18 weeks
Mean change in Pediatric Quality of Life Inventory (PedsQL) score between baseline, week 14 and week 18.	Mean change in PedsQL score will be compared between baseline, week 14 to evaluate supplementation effects and week 18 to verify persistence of treatment effects after wash-out (product cessation). PedsQ consists in 23 items and four subscales: physical functioning, emotional functioning, social functioning and school functioning. A higher score represents better health related QoL.	Baseline, 14 weeks and 18 weeks
Mean change in Parenting Stress Index-Short Form (PSI-SF) score between baseline, week 14 and week 18.	Mean change in PSI-SF score will be compared between baseline, week 14 to determine supplementation effects and week 18 to verify persistence of treatment effects after wash-out (product cessation). It is divided into three domains: parental distress, dysfunctional parent-child interaction and difficult child, with a total score ranging from 36 to 180. A higher score indicates a higher clinical level of distress.	Baseline, 14 weeks and 18 weeks

Collaborators and Investigators

• Sponsor: Valérie Marcil
• Collaborators: University of Ottawa; Institut universitaire de cardiologie et de pneumologie de Québec, University Laval; Institut National de la Recherche Scientifique - Centre Armand Frappier Santé Biotechnologie; Hôpital du Sacré-Coeur de Montréal (CIUSSS - NIM)
• Investigators: Principal Investigator: Valérie Marcil, Professor, St. Justine's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 2, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Microbiota; Probiotics; Autism Spectrum Disorder; Gastrointestinal symptoms; Sleep disorder
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autism Spectrum Disorder; Autistic Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: 2025-8319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD might be shared to other research upon resonable request to the Principal Investigator/Sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No