Effects of Lactobacillus Plantarum PS128 in Children With ASD

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Lactobacillus Plantarum PS128 in Children With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Dietary Supplement: PS128
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PS128<br>Subjects will take PS128 capsules every day (2 capsules/day, once) for 12 weeks. | Dietary Supplement: PS128<br>* Each PS128 capsule contained >3 × 10^10 colony forming units (CFU) with microcrystalline cellulose and weights 425 ± 25 mg.<br>|
| Placebo Comparator: Placebo<br>Subjects will take placebo capsules every day (2 capsules/day, once) for 12 weeks. | Other: Placebo<br>* The placebo capsules only contained 425 ± 25 mg microcrystalline cellulose.<br>|
| 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 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 |