Autism Spectrum Disorder
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTPS128
Each PS128 capsule contained \>3 × 10\^10 colony forming units (CFU) with microcrystalline cellulose and weights 425 ± 25 mg.
OTHERPlacebo
The placebo capsules only contained 425 ± 25 mg microcrystalline cellulose.
Sponsors
Chang Gung Memorial Hospital
Bened Biomedical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 12 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Total Scores of Social Responsiveness Scale | Baseline, Week 12 and Week 16 | Social Responsiveness Scale can measure the autism clinical severity with the range from 65-260. The lower scores stand for better social responsiveness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Total Scores of Parenting Stress Index, Fourth Editon | Baseline, Week 12 and Week 16 | Parenting Stress Index is a parents' report questionnaire for parenting stress. The score ranges from 0-180. The lower scores stand for lower parenting stress. |
| Changes of Total Scores of Aberrant Behavior Checklist | Baseline, Week 12 and Week 16 | Aberrant Behavior Checklist is a parents' report questionnaire for aberrant behavior. The score ranges from 0-174. The lower scores stand for less aberrant behavior. |
| Changes of Total Scores of Repetitive Behavior Scale-Revised | Baseline, Week 12 and Week 16 | 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. |
| Changes of Total Scores of Child Behavior Checklist | Baseline, Week 12 and Week 16 | Child Behavior Checklist is a parents' report questionnaire for behavioral and emotional problems. The score ranges from 0-240. The lower scores stand for better behavioral and emotional regulation. |
| Changes of Total Scores of Adaptive Behavior Assessment System | Baseline, week 12 and Week 16 | 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. |
| Changes in Accuracy of Frith-Happe Animation | Baseline, Week 12 and Week 16 | A quick and objective test of Theory of Mind. 8 questions in total, the more correct questions stand for better Social Cognition. |
| Changes in Accuracy of Eyes Task | Baseline, Week 12 and Week 16 | An advanced test for Theory of Mind. 43 questions in total, the more correct questions stand for better social skills. |
| Assessment of Clinical Global Impression-Severity of Illness | Week 12 and Week 16 | 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. The score ranges from 1-7. 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. |
| Assessment of Patient Global Impression of Change | Week 12 and Week 16 | 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. The score ranges from 1-7. Patients rate their change as "1=very much improved ," "2=much improved," "3=minimally improved," "4=no change," "5=minimally worse," "6=much worse," or "7=very much worse)." |
| Gut Microbiota-Relative Abundance of Bifidobacterium Faecale | Baseline and Week 12 | 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. Values represent percentages and range from 0 to 100%, with higher values indicating a higher relative abundance of the target bacterium in the gut microbiota |
| MRI T1 | Baseline and Week 12 | Brain structural volumes (cm²). The advanced processing and analysis of the MRI data have been outsourced to an external core facility. Due to resource scheduling and the prolonged timeline required for specialized image preprocessing, the data analysis is currently in progress and has not yet been finalized. Therefore, quantifiable results are unavailable for summary in the data table at this time. |
| Functional MRI (Resting-state/Biological Motion Task) - BOLD Signal | Baseline and Week 12 | Blood-oxygen-level-dependent (BOLD) signal is a measurement used in fMRI, which reflects the neural activity. The advanced processing and analysis of the MRI data have been outsourced to an external core facility. Due to resource scheduling and the prolonged timeline required for specialized image preprocessing, the data analysis is currently in progress and has not yet been finalized. Therefore, quantifiable results are unavailable for summary in the data table at this time. |
| Diffusion Tensor Imaging (DTI) - FA | Baseline and Week 12 | 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. The advanced processing and analysis of the MRI data have been outsourced to an external core facility. Due to resource scheduling and the prolonged timeline required for specialized image preprocessing, the data analysis is currently in progress and has not yet been finalized. Therefore, quantifiable results are unavailable for summary in the data table at this time. |
| Safety Assessment - Albumin | Baseline and Week 12 | Safety is assessed function of liver and kidney such as albumin (3.5-5.4 g/dl). |
| Safety Assessment - Total Protein | Baseline and Week 12 | Safety is assessed function of liver and kidney such as total protein (6.4-8.3 g/dl). |
| Safety Assessment - ALP | Baseline and Week 12 | Safety is assessed function of liver and kidney such as ALP (135-320 U/L). |
| Safety Assessment - Total Bilirubin | Baseline and Week 12 | Safety is assessed function of liver and kidney such as total bilirubin (0.3-1.2 mg/dl). |
| Safety Assessment - T-Cholesterol | Baseline and Week 12 | Safety is assessed function of liver and kidney such as T-Cholesterol (\<170 mg/dL). |
| Safety Assessment - Uric Acid | Baseline and Week 12 | Safety is assessed function of liver and kidney such as uric acid (\<7.0 mg/dl). |
| Safety Assessment - BUN | Baseline and Week 12 | Safety is assessed function of liver and kidney such as BUN (7-25 mg/dl). |
| Safety Assessment - Creatinine | Baseline and Week 12 | Safety is assessed function of liver and kidney such as creatinine (0.2-1.0 mg/dl). |
| Safety Assessment - AST | Baseline and Week 12 | Safety is assessed function of liver and kidney such as AST (13-40 U/L). |
| Safety Assessment - ALT | Baseline and Week 12 | Safety is assessed function of liver and kidney such as ALT (7-40 U/L). |
| Change in Levels of Exploratory Blood-based Biomarkers for Inflammatory Changes - MPO | Baseline and Week 12 | Inflammatory is assessed via a composite measure of circulating cytokines - MPO (ng/mL) |
| Change in Levels of Exploratory Blood-based Biomarkers for Inflammatory Changes - IL-1β | Baseline and Week 12 | Inflammatory is assessed via a composite measure of circulating cytokines - IL-1β (pg/mL) |
| Change in Levels of Exploratory Blood-based Biomarkers for Inflammatory Changes - TGF-β1 | Baseline and Week 12 | Inflammatory is assessed via a composite measure of circulating cytokines - TGF-β1 (pg/mL) |
| Change in Levels of Exploratory Blood-based Biomarkers for Inflammatory Changes - Eotaxin | Baseline and Week 12 | Inflammatory is assessed via a composite measure of circulating cytokines - Eotaxin (pg/mL) |
| Change in Levels of Exploratory Blood-based Biomarkers for Inflammatory Changes - IL-6 | Baseline and Week 12 | Inflammatory is assessed via a composite measure of circulating cytokines - IL-6 (ng/mL) |
| Change in Levels of Exploratory Blood-based Biomarkers for Oxidative Stress Changes - Serotonin | Baseline and Week 12 | Oxidative stress is assessed via Serotonin (ng/mL). |
| Change in Levels of Exploratory Blood-based Biomarkers for Oxidative Stress Changes - GABA | Baseline and Week 12 | Oxidative stress is assessed via GABA (μmol/L). |
| Change in Levels of Exploratory Blood-based Biomarkers for Oxidative Stress Changes - Cortisol | Baseline and Week 12 | Oxidative stress is assessed via Cortisol (6-10am 4.82-19.5, 4-8pm 2.47-11.9, μg/dl). |
| Changes of Total Scores of Emotional Dysregulation Inventory | Baseline, Week 12 and Week 16 | 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. |
| Gut Microbiota-Relative Abundance of Lactiplantibacillus Plantarum | Baseline and Week 12 | 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. Values represent percentages and range from 0 to 100%, with higher values indicating a higher relative abundance of the target bacterium in the gut microbiota. |
Countries
Taiwan
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 8.9 years STANDARD_DEVIATION 1.6 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 17 | 0 / 0 |
| other Total, other adverse events | 0 / 19 | 0 / 17 | 0 / 0 |
| serious Total, serious adverse events | 0 / 19 | 0 / 17 | 0 / 0 |
Outcome results
None listed