Psychophysiological Effects of Lactobacillus Plantarum PS128 in Preschool Children With Autism Spectrum Disorder

Study Overview
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Brief Summary
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Autism Spectrum Disorders (ASD) comprises a complex group of disorders of neuronal development characterized by social and communication impairment along with presence of repetitive and restrictive behaviors. Emerging evidences support the gut-brain axis and further microbiota-gut-brain axis. Elevated prevalence of gastrointestinal (GI) dysfunction in individuals with ASD suggested that targeting gut may benefit patients with ASD. Lactobacillus plantarum PS128 (PS128) was reported to be a psychobiotic in several animal studies which modulated the levels of neurotransmitters in different brain areas. The current randomized, placebo-controlled trial was conducted to investigate the psychophysiological effects of PS128 in preschool children with ASD.

Detailed Description
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Emerging evidences support the gut-brain axis and further microbiota-gut-brain axis. Elevated prevalence of gastrointestinal (GI) dysfunction in individuals with ASD suggested that targeting gut may benefit patients with ASD. Lactobacillus plantarum PS128 (PS128) was reported to be a psychobiotic in several animal studies which modulated the levels of neurotransmitters in different brain areas. The current randomized, placebo-controlled trial was conducted to investigate the psychophysiological effects of PS128 in preschool children with ASD.

Official Title
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Psychophysiological Effects of Lactobacillus Plantarum PS128 in Preschool Children With Autism Spectrum Disorder: a Randomized, Placebo-controlled Trial

Conditions
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Autism

Intervention / Treatment
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* Other: Probiotic, Lactobacillus plantarum PS128
* Other: Placebo, microcrystalline cellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-V) criteria of Autism Spectrum Disorder Do not take any other probiotics for at least 3 weeks before and during the study period Exclusion Criteria: Autistic children with other neurodevelopmental disorders or psychiatric diseases With a clinically significant chronic medical condition, including; anemia, brain malformations, metabolic diseases, epilepsy, organic gastrointestinal disorders (i.e. gastroesophageal reflux, food allergies, irritable bowel syndrome (IBS)) and Celiac disease On anti-fungal, antibiotics, special diet (i.e. gluten-free diet, casein-free diet, high-protein diet, ketogenic diet) and current use of psychiatric medications within the preceding 3 weeks were excluded Known allergy to probiotics

Ages Eligible for Study
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Minimum Age: 30 Months
Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blinded, randomized, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactobacillus plantarum PS128 (PS128)<br>Subjects will receive oral Lactobacillus plantarum PS128 capsules, 2 capsules per day, for 16 weeks. | Other: Probiotic, Lactobacillus plantarum PS128<br>* PS128 capsules, 2 capsules per day<br>* Other names: PS128;|
| Placebo Comparator: Placebo<br>Subjects will receive oral placebo capsules, 2 capsules per day, for the first 8 weeks. The following 8 weeks, subjects will receive oral Lactobacillus plantarum PS128 capsules, 2 capsules per day, for 8 weeks. | Other: Placebo, microcrystalline cellulose<br>* Placebo capsules, 2 capsules per day<br>* Other names: Placebo;|
| No Intervention: Normal Control<br>Normal control group are enrolled by invitation from the age and gender matched healthy children. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline of anxiety subscale in Children's Behavior Checklist (CBCL)/Achenbach System of Empirically Based Assessment (ASEBA) at week 8 and week 16 | ASEBA for behavioral assessment | Baseline, week 8 and week 16 | 
| Changes from hyperactivity subscale of Attention-Deficit/Hyperactivity Disorder Test (ADHDT) at week 8 and week 16 | Inattention, hyperactive symptoms evaluation | Baseline, week 8 and week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal symptoms recorded by using GI Severity Index (6-GSI) at week 8 and week 16 | constipation, diarrhea, stool consistency, stool smell, flatulence, and abdominal pain | Baseline, week 8 and week 16 | 
| Change of total scores at week 8 and week 16 from baseline of Changes of Childhood Asperger Syndrome Test (CAST) | CAST for behavioral assessment | Baseline, week 8 and week 16 | 
| Change of total scores at week 8 and week 16 from baseline of Penn Interactive Peer Play Scale, (PIPPS) | PIPPS for communicative and interactive assessment | Baseline, week 8 and week 16 | 
| Change of total scores at week 8 and week 16 from baseline of Social Interaction Assessment Scale | Communicative and interactive assessment | Baseline, week 8 and week 16 | 
| Comparison of Microbiota composition between week 8 and baseline | Gut and oral microbiota analysis | Baseline and week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autism, preschool children