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

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

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.

Study Overview

• Status: Unknown
• Conditions: Autism
• Intervention / Treatment: Other: Probiotic, Lactobacillus plantarum PS128; Other: Placebo, microcrystalline cellulose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui-Ju Chen MD; Phone Number: 02-25433535; Email: hjuchen0623@gmail.com
• Study Contact Backup: Name: Hui-Ju Chen MD; Phone Number: 02-25433535; Email: mmhcto@gmail.com; a6284@mmh.org.tw

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Department of Pediatric Neurology, MacKay Children's Hospital
    • Contact: Hui-Ju Chen; Phone Number: 02-25433535; Email: hjuchen0623@gmail.com
    • Principal Investigator: Hui-Ju Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lactobacillus plantarum PS128 (PS128); Subjects will receive oral Lactobacillus plantarum PS128 capsules, 2 capsules per day, for 16 weeks.	Other: Probiotic, Lactobacillus plantarum PS128; PS128 capsules, 2 capsules per day; Other Names: PS128
Placebo Comparator: Placebo; 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; Placebo capsules, 2 capsules per day; Other Names: Placebo
No Intervention: Normal Control; Normal control group are enrolled by invitation from the age and gender matched healthy children.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mackay Memorial Hospital
• Investigators: Principal Investigator: Hui-Ju Chen MD, Department of Pediatric Neurology, MacKay Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: June 10, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: autism; preschool children
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder
• Other Study ID Numbers: 17MMHIS193e

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No