Clinical trial NCT04948814: Application of Fecal Microbiota Transplantation in Children With ASD
Official title: Clinical Trial of Fecal Microbiota Transplantation in Children With Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder，Fecal microbiota transplantation
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2021-07-02
Enrollment: 40
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Autism Spectrum Disorder (ASD) is a group of serious neurodevelopmental disorders. Intestinal microbial disturbance is common in children with ASD, and about 40% of ASD children suffer from gastrointestinal dysfunction. A great deal of evidence shows that intestinal microbes can influence the brain to play its role through "brain-intestinal-microbiota axis". Fecal microbial biota transplantation (FMT) is the most direct way to change the intestinal flora rapidly. We intend to study the difference of intestinal flora structure and metabolism between ASD children and control children at the level of phylum, genus and species; To explore the role of fecal bacteria transplantation in improving core symptoms and gastrointestinal dysfunction of children in autism spectrum disorder; To study the potential etiological mechanism of autism spectrum disorder.

Detailed description: 20 ASD children and 20 healthy children who are 3 to 18 years of age will be enrolled in the trial. The fecal donors who are 20 healthy children, will be extensively screened for infectious diseases prior to providing stool for the transplant. After being informed about the study and potential risks, all patients giving written informed consent will undergo screening period to determine eligibility for study entry. 20 ASD children who meet the eligibility requirements will receive a fecal microbiota transplantation following a 2-week treatment with Vancomycin. Fecal bacteria transplantation will be achieved through nasogastric tube, nasojejunal tube, esophagogastroduodenoscopy, colonoscopy or enema. The amount of fecal bacterial liquid transplantation for children is 5ml/kg each time. Microbiota analysis will also be performed on both the donor and recipient stool sample prior to transplantation, and on the recipient sample at 1 month, 3 month and 6 months post transplantation. We evaluate the difference of intestinal flora structure and metabolism between ASD children and control children at the level of phylum, genus and species, and explore the role of fecal bacteria transplantation in improving core symptoms and gastrointestinal dysfunction of children in autism spectrum disorder.

Eligibility criteria: Inclusion criteria for ASD children.

1. Children who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and ADOS-2 diagnostic criteria.
2. Age 3-18 years.

Inclusion criteria for donor.

1. Children who match ASD children in age and gender, preferably from relatives.
2. No antibiotic treatment in the last 3 months.
3. Children who are healthy in growth and development, with normal results of child developmental and neuropsychological tests, including ASD-related screening, Attention-deficit hyperactivity disorder (ADHD)-related screening and motor screening.
4. Children who have normal serological test results, including pre-transfusion testing, liver and kidney function, hepatitis B detection, quantification of hepatitis C, quantification of A virus immunoglobulin M (HAV-IgM), Epstein-Barr virus DNA (EBV-DNA) and Human Immunodeficiency Virus (HIV), detection of microvirus B19, TORCH, tuberculosis infection T-cell test (T-SPOT), total total immunoglobulin E (IgE), food and inhalant allergen testing, and lymphocyte subpopulation analysis.
5. Children who have normal stool test results, including fecal routine and fecal occult blood, bacteria (Clostridium difficile A/B toxin, Escherichia coli O157, Shigella spp., Salmonella spp., Campylobacter spp., Staphylococcus aureus, Yersinia spp., Vibrio parahaemolyticus, Cholera isolates), fungi (Pseudomonas albicans, etc.), viruses (rotavirus, etc.), parasites (Giardia lamblia, Cryptosporidium, Cyclospora).
6. Children who have normal results for chest X-ray, abdominal ultrasound, C13 breath test, cranial MRI, etc.

Exclusion criteria for ASD children.

1. ASD children with severe gastrointestinal symptoms or organic disease requiring immediate surgery or treatment.
2. ASD children who have received antibiotics within 3 months, or are receiving immunosuppressive agents and biologics.
3. ASD children with underlying diseases, such as severe anemia, malnutrition, autoimmune diseases (autoimmune thyroiditis, type I diabetes, etc.), allergic diseases (asthma, severe eczema, etc.), central nervous system diseases, metabolic syndrome, etc.
4. ASD children with other organic dysfunctions, such as cerebral palsy, congenital genetic diseases, etc.; history of other psychiatric-behavioral disorders, genetic-metabolic diseases and other major physical diseases; other physical diseases, such as hearing impairment, vocal disorders, blindness, etc.

Exclusion criteria for donor.

1. Children who have functional gastrointestinal symptoms suggested by the Rome IV diagnostic questionnaire for functional gastrointestinal disorders.
2. Children who have gastrointestinal disorders, including gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain, bloating, diarrhea, constipation, etc.), chronic gastrointestinal disorders (chronic diarrhea, chronic abdominal pain, etc.), gastroesophageal reflux disease, peptic ulcer, a history of gastrointestinal surgery (intestinal obstruction, megacolon, pyloric stenosis, etc.)
3. Children who suffer from other diseases, including familial autoimmune diseases such as type I diabetes, inflammatory bowel disease, rheumatoid arthritis, chronic lymphocytic thyroiditis (Hashimoto's disease), toxic diffuse goiter (Graves' disease), etc.;
4. Children who have received drugs that has impact on the intestinal microbiota (such as proton pump inhibitors, pro-gastrointestinal drugs, steroids, aspirin, etc.) within six months.
5. Children who have received antibiotics within three months;
6. Children who are receiving immunosuppressants and biological agents.
7. Children who are undergoing chemotherapy for various tumors;
8. Children who have liver and kidney diseases, central nervous system diseases, acute and chronic infectious diseases (tuberculosis, measles, syphilis, HIV, etc.), severely anemic, malnourished, metabolic syndrome (obesity, diabetes, etc.),
9. Children who live in a place with prevalence of bacterial, viral, parasitic, etc.

Primary outcomes:
measure: Change in Autism Diagnostic Observation Scale (ADOS) in ASD children
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Changes in the Autism Behavior Checklist (ABC) in ASD children
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Changes in the Childhood Autism Rating Scale (CARS) in ASD children
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Change in Social Responsiveness Scale (SRS) in ASD children
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Change in Autism Treatment Evaluation Checklist (ATEC) in ASD children
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Change in gastrointestinal symptoms among children with ASD
timeFrame: baseline, 2 weeks, 5 weeks , 8 weeks , 10 weeks , 12 weeks and 14 weeks, and 1 month, 3 month, 6 months post transplantation
measure: Evaluate the difference of the gut microbe composition between children with ASD and healthy children by sequencing faecal metagenome.
timeFrame: 6 months post transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
References:
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