Autism Spectrum Disorder
Conditions
Brief summary
Autism spectrum disorders (ASD) are a group of severe neurodevelopmental conditions characterized by impaired communication and social interaction, as well as repetitive/stereotyped behaviors deriving from a combination of genetic and environmental factors. The ASD diagnosis rates increased dramatically over the past number of decades. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) describes a worldwide prevalence of approximately 1%. The prevalence of ASD is 1 in 59 individuals in the US reported by the Centers for Disease Control and Prevention. According to the latest data from the Italian National Observatory for ASD, the actual prevalence in Italy is about 1/77 for children aged between 7 and 9 years, with a 4.4 times higher prevalence in male. The origin of ASD is still largely undefined. It has been hypothesized a possible role for the influence of early life alteration of gut microbiome (GM). We demonstrated an imbalance in Bacteroidetes and Firmicutes phyla with a decrease in Bacteroidetes/Firmicutes ratio in the GM of pediatric patients affected by ASD. Similar data have been observed by others. Data from ASD animal model confirm the presence of GM dysbiosis with significant correlation with behavioral, gastrointestinal and immunologic alterations. Altogether these data support the hypothesis that GM dysbiosis could be involved in the ASD pathogenesis. The ASD children present an increased prevalence of functional gastrointestinal disorders (FGIDs), mainly chronic constipation, functional diarrhea, and irritable bowel syndrome (IBS). A role for GM has been suggested also for these conditions. The presence of these disorders negatively influence the disease severity and the parental quality of life of ASD children. Starting from all these considerations GM is becoming a possible target of intervention for pediatric ASD. Probiotics are one of the most investigated strategy for a beneficial modulation of GM. Probiotics are commonly defined as live microorganisms which when ingested in adequate amounts confer a beneficial effect on the host. The most used probiotics in the pediatric age are Saccharomyces and Lactobacillus strains including Lactobacillus rhamnosus GG (LGG). Data report a beneficial influence elicited by LGG on GM structure and function. This probiotic resulted also effective in treating FGIDs patients. Preliminary evidence suggest the potential efficacy of probiotics for FGIDs treatment in ASD children. Altogether these evidence strongly support the hypothesis that LGG could exert a beneficial action in ASD children. The purpose of this study is to evaluate the therapeutic efficacy of LGG on FGIDs in ASD children.
Interventions
Lactobacillus rhamnosus GG
OTHERPlacebo
Placebo
Sponsors
Federico II University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
4 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* children aged 4-12 years * children of both sex * children with a sure diagnosis of ASD and presence of FGIDs with a GSI ≥7 from at least 3 months.
Exclusion criteria
* children aged \<4 or \>12 years * uncertain ASD and/or FGIDs diagnosis * FGIDs duration lasting \<3 months * concomitant presence of other chronic conditions (adverse food reactions; genetic and metabolic disorders; malformations of GI, respiratory or urinary tract; neurologic diseases; immunodeficiencies; diabetes; cardiovascular diseases; autoimmune diseases; chronic infections; chronic respiratory, GI or urinary tract diseases; obesity; tumors; malnutrition). * use of antibiotics and/or pre-/pro-/ synbiotics during the 6 months prior to enrolment * participation into other clinical trials during the last 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional gastrointestinal disorders (FGIDs) severity | At 16 weeks of treatment | Severity index of gastrointestinal symptoms (GI Severity Index, GSI) - Minimum Score: 0 (Indicates absence of gastrointestinal symptoms or optimal bowel regularity) Maximum Score: 17 (Represents the highest severity of symptoms reported in the questionnaire) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of the LGG impact on FGIDs | At baseline and at 4 weeks and 12 weeks from the end of treatment | Changes in the GSI - Minimum Score: 0 (Indicates absence of gastrointestinal symptoms or optimal bowel regularity) Maximum Score: 17 (Represents the highest severity of symptoms reported in the questionnaire) |
| Gut Microbiome (GM) composition | At baseline and at 16 weeks of treatment | Shotgun metagenomics analysis |
| GM function: fecal short chain fatty acids (SCFAs) levels | At baseline and at 16 weeks of treatment | Gas chromatograph(GC)-mass spectrometry (MS) analysis |
| ASD children behavior | At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment | Aberrant Behavior Checklist (ABC) questionnaire - Minimum Score: 0 (Indicates the complete absence of aberrant or problematic behaviors in the assessed areas, e.g., aggression, social withdrawal, stereotypies, etc.) Maximum Score: 174 (Represents the highest severity and frequency of problematic behaviors reported in the test. All listed aberrant behaviors-such as self-injury, severe hyperactivity, complete social withdrawal, and repetitive speech-are present at maximum intensity.) |
| Kinetics of Lactobacillus rhamnosus GG (LGG) | At baseline and at 4 weeks, 8 weeks and 12 weeks of treatment | Using the GI Severity Index (GSI) - Minimum Score: 0 (Indicates absence of gastrointestinal symptoms or optimal bowel regularity) Maximum Score: 17 (Represents the highest severity of symptoms reported in the questionnaire) |
| Body weight | At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment | Body weight will be evaluated in kilograms |
| Height | At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment | Body weight will be evaluated in cm |
| Infectious diseases | At 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment | It will be assessed the number of infectious episodes, type of infectious diseases, need for drugs |
| Parental quality of life | At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment | EUROHIS QOL-8 questionnaire - Minimum Score: 8 (Indicates the lowest level of satisfaction and quality of life) Maximum Score: 40 (Indicates the highest level of satisfaction and quality of life) |
Countries
Italy
Outcome results
None listed