Effects of Lactobacillus Plantarum PS128 in Children With ASD

Effects of Lactobacillus Plantarum PS128 in Children With Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral deficits. Probiotics are regarded as active microorganisms. With sufficient amounts, probiotics can regulate intestinal flora, intestinal permeability, inflammation and antioxidant reactions in the body. These reactions may further promote health, regulate metabolic disease progression and prevent complications. Lactobacillus plantarum PS128 (PS128) was reported to be a psychobiotic in several animal and human studies which modulated the levels of neurotransmitters in different brain areas. This study is to evaluate whether the consumption of PS128 can improve the symptoms of patients with ASD. The current randomized, placebo-controlled trial was conducted to investigate the psychophysiological effects of PS128 in school children with ASD.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Dietary supplement: PS128; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hsing-Chang Ni, Dr.; Phone Number: 3815 88633281200; Email: alanni0918@yahoo.com.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Hsing Chang Ni; Phone Number: 2479 886-3-3281200; Email: alanni0918@yahoo.com.tw
    • Principal Investigator: Hsing Chang Ni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 12 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• (1) Age 7 to 12 years old.
• (2) PS128 group and placebo group: Children with autism spectrum disorder, confirmed by Autism Diagnostic Observation Schedule.
• (3) Normal control group: Children without autism spectrum disorder.

Exclusion Criteria:

• (1) Receiving antibiotics within one month.
• (2) Probiotics used in powder, capsule, or tablet in two weeks (except for Yogurt, Yogurt, Yakult and other related foods).
• (3) Patients with hepatobiliary gastrointestinal tract who have undergone surgery (except for hernia surgery and appendectomy)
• (4) Those with special diets (gluten-free, casein-free, high-protein, and ketogenic diet).
• (5) Those with a history of cancer.
• (6) Those who are allergic to lactic acid bacteria.
• (7) Not eligible judged by PI

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PS128; Subjects will take PS128 capsules every day (2 capsules/day, once) for 12 weeks.	Dietary supplement: PS128; Each PS128 capsule contained >3 × 10^10 colony forming units (CFU) with microcrystalline cellulose and weights 425 ± 25 mg.
Placebo Comparator: Placebo; Subjects will take placebo capsules every day (2 capsules/day, once) for 12 weeks.	Other: Placebo; The placebo capsules only contained 425 ± 25 mg microcrystalline cellulose.
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 of total scores of Social Responsiveness Scale	Social Responsiveness Scale can measure the autism clinical severity with the range from 65-260. The lower scores stand for better social responsiveness.	Baseline, Week 12 and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of total scores of Repetitive Behavior Scale-Revised	Repetitive Behavior Scale-Revised is a questionnaire that focuses on repetitive behavior. The score ranges from 0-129. The lower scores stand for lower repetitive behavior.	Baseline, Week 12 and Week 16
Changes of total scores of Child Behavior Checklist	Child Behavior Checklist is a parents' report questionnaire for behavioral and emotional problems. The lower scores stand for better behavioral and emotional regulation.	Baseline, Week 12 and Week 16
Changes of total scores of Adaptive Behavior Assessment System	Adaptive Behavior Assessment System is a parents' report questionnaire for adaptive behavior. The score ranges from 9-171. The higher scores stand for better adaptive behavior.	Baseline, week 12 and Week 16W
Changes in accuracy of Frith-Happe animation	A quick and objective test of Theory of Mind. 8 questions in total, the more correct questions stand for better Social Cognition.	Baseline, Week 12 and Week 16
Changes in accuracy of Eyes task	An advanced test for Theory of Mind. 43 questions in total, the more correct questions stand for better social skills.	Baseline, Week 12 and Week 16
Changes of total scores of Aberrant Behavior Checklist	Aberrant Behavior Checklist is a parents' report questionnaire for aberrant behavior. The lower scores stand for less aberrant behavior.	Baseline, Week 12 and Week 16
Visual Analogue Scale for GI symptoms	Visual Analogue Scale for GI symptoms was designed to measure the response of symptoms and well-being in patients after taking PS128. The score ranges from 0-10. The lower scores stand for less GI symptoms.	Baseline, week 12 and Week 16
Changes of total scores of Emotional Dysregulation Inventory	Emotional Dysregulation Inventory is a parents' report questionnaire for emotional dysregulation. The score ranges from 0-120. The lower scores stand for better emotional regulation.	Baseline, Week 12 and Week 16
Changes of total scores of Parenting Stress Index, Fourth Editon	Parenting Stress Index is a parents' report questionnaire for parenting stress. The lower scores stand for lower parenting stress.	Baseline, Week 12 and Week 16
Assessment of Clinical Global Impression-Severity of Illness	The Clinical Global Impression (CGI) is a clinician rated measure of illness severity, improvement, and efficacy of treatment. The CGI-I is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse.	Baseline, Week 12 and Week 16
Assessment of Patient Global Impression of Change	The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."	Week 12 and Week 16
Gut microbiota	Collect the DNA of fecal flora to test the diversity and abundance of gut microbiota as well as short chain fatty acids in Stool samples. The 16S rRNA gene amplicons will be prepared following the Illumina protocol for preparing the 16S metagenomic sequencing library.	Baseline and Week 12
MRI T1	Brain structural volumes (cm²)	Baseline and Week 12
functional MRI (resting-state/biological motion task) - BOLD signal	Blood-oxygen-level-dependent (BOLD) signal is a measurement used in fMRI, which reflects the neural activity.	Baseline and Week 12
Diffusion Tensor Imaging (DTI) - FA	Fractional anisotropy (FA) is a measurement used in DTI, which reflects the movement of water molecules. FA ranges from 0 to 1, the higher FA value may represent more intact axons.	Baseline and Week 12
Safety assessment - Albumin	Safety is assessed function of liver and kidney such as albumin (6.6-8.7 g/dl).	Baseline and Week 12
Safety assessment - Total Protein	Safety is assessed function of liver and kidney such as total protein (3.8-5.3 g/dl).	Baseline and Week 12
Safety assessment - ALP	Safety is assessed function of liver and kidney such as ALP (40-129 IU/L).	Baseline and Week 12
Safety assessment - Total Bilirubin	Safety is assessed function of liver and kidney such as total bilirubin (0.2-1.2 mg/dl).	Baseline and Week 12
Safety assessment - T-Cholesterol	Safety is assessed function of liver and kidney such as T-Cholesterol (<170 mg/dL).	Baseline and Week 12
Safety assessment - Uric Acid	Safety is assessed function of liver and kidney such as uric acid (3.4-7.6 mg/dl).	Baseline and Week 12
Safety assessment - BUN	Safety is assessed function of liver and kidney such as BUN (6-20 mg/dl).	Baseline and Week 12
Safety assessment - Creatinine	Safety is assessed function of liver and kidney such as creatinine (0.6-1.3 mg/dl).	Baseline and Week 12
Safety assessment - AST	Safety is assessed function of liver and kidney such as AST (8-38 IU/L).	Baseline and Week 12
Safety assessment - ALT	Safety is assessed function of liver and kidney such as ALT (4-44 IU/L).	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for inflammatory changes - MPO	Inflammatory is assessed via a composite measure of circulating cytokines - MPO (ng/mL)	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for inflammatory changes - IL-1β	Inflammatory is assessed via a composite measure of circulating cytokines - IL-1β (pg/mL)	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for inflammatory changes - TGF-β1	Inflammatory is assessed via a composite measure of circulating cytokines - TGF-β1 (pg/mL)	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for inflammatory changes - Eotaxin	Inflammatory is assessed via a composite measure of circulating cytokines - Eotaxin (pg/mL)	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for inflammatory changes - IL-6	Inflammatory is assessed via a composite measure of circulating cytokines - IL-6 (ng/mL)	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for oxidative stress changes - Serotonin	Oxidative stress is assessed via Serotonin (ng/mL).	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for oxidative stress changes - GABA	Oxidative stress is assessed via GABA (umol/L).	Baseline and Week 12
Change in levels of exploratory blood-based biomarkers for oxidative stress changes - Cortisol	Oxidative stress is assessed via Cortisol (nmol/L).	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Bened Biomedical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: 202101416A3

Drug and device information, study documents

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