AutismNCT04890717
Biomarkers for Autism and ADHD in Children
An observational study of Autism and ADHD, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Autism (ASD) is one of the frequent neurodevelopmental disorders that children would occur. Many studies have shown that individuals with Autism are more common to experience significant gastrointestinal problems than other individuals. Symptoms include constipation, diarrhea, abdominal pain and gastric reflux. Read more about this study
- Who is it for?
- Ages Up to 18 years
- How many people
- 320 participants
- Where
- 1 siteHong Kong
- Study dates
- 15 May 2021to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Subjects include * suspected or confirmed cases of ASD and/or ADHD children (Case group), * typically developed siblings of suspected or confirmed cases of ASD and/or ADHD children (Sibling group), * parents of suspected or confirmed cases of ASD and/or ADHD children (Parent group) * typically developed children not related to the case group (Control Group).
Who may be able to join
- Case group, Sibling group and Control group:
- Children aged under 18 years old; and
- The parents or legal guardian agree to hand in the stool samples of children; and agree to complete questionnaires; and
- The parents or legal guardian agree to sign the informed consent form for the children
- Parent group:
- Their suspected or confirmed ASD or ADHD children participated in the study; and
- Agree to hand in stool samples and complete questionnaires; and
- Agree to sign the informed consent consent
Who cannot join
- All groups:
- Any subject taken probiotics, prebiotics, antibiotics 30 days before enrollment.
- Subjects can be re-approached or join the study 30 days after taking probiotics, prebiotics, antibiotics.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong
Siew Chien Ng, PhD, 35053996, siewchienng@cuhk.edu.hk
About this study
Official title: Microbial Stool Biomarkers for Prediction of Autism and ADHD in Children
Autism (ASD) is one of the frequent neurodevelopmental disorders that children would occur. Many studies have shown that individuals with Autism are more common to experience significant gastrointestinal problems than other individuals. Symptoms include constipation, diarrhea, abdominal pain and gastric reflux. A recent study with 50 children with ASD, 50 children with other developmental disabilities and 50 healthy control children, it found that 70% of ASD children had presented with GI symptoms, compared with 42% of developmental disabilities children and 28% of developing children, it is believed that ASD children will have a distinctive microbial pattern in the stool.
Attention-deficit/hyperactivity disorder (ADHD) is another neurodevelopmental and neurobehavioral disorder. A study found that ADHD individuals experience significantly higher rate of stomach pain and bowel problems than other control individuals. It is suggested that the microbiota in the stool of ADHD children might be different. Genetic study also found that if a child has a sibling with ADHD, the risk of developing ADHD is three to four times higher than that of children with siblings without ADHD.
Read the detailed description
Autism Spectrum Disorder (ASD) was first developed by Kanner in 1943. In Hong Kong, a study showed that as many as 49 out of 10,000 children were diagnosed in Autism. ASD is one of the frequent neurodevelopmental disorders that children would occur. Many studies have shown that individuals with Autism are more common to experience significant gastrointestinal problems than other individuals. Symptoms include constipation, diarrhoea, abdominal pain and gastric reflux. In a study with 160 children with ASD, 59% had GI symptoms, including diarrhoea, unformed stool, constipation, bloating and gastroesophageal reflux (GERD). A study compared 51 ASD children, and 40 healthy control children found that 63% of ASD children had moderate or severe diarrhoea and constipation symptoms. In contrast, only 2% of control children had such experience. Similarly, a study of 150 children, with 50 children with ASD, 50 children with other developmental disabilities and 50 healthy control children, it found that 70% of ASD children had presented with GI symptoms, compared with 42% of developmental disabilities children and 28% of developing children. Other study stated that such untreated GI symptoms might worsen the behavioural issue of ASD children. As there is a strong relationship between ASD children and GI symptoms, it is believed that ASD children will have a distinctive microbial pattern in the stool.
Attention-deficit/hyperactivity disorder (ADHD) is another neurodevelopmental and neurobehavioral disorder. In Hong Kong, there were 8.9% of ADHD children among Primary one Chinese schoolboys. A large study (N=6483) found that ADHD individuals experience a significantly higher rate of stomach pain and bowel problems than other control individuals. McKeown did another study also reported that ADHD children were more likely to experience constipation and stool incontinence than normal healthy children. In one study that compared the Gastrointestinal Severity Index scoring between children with ADHD and healthy subjects, children with ADHD had significantly higher mean and scored higher in constipation, diarrhoea and flatulence variables. As the findings of ADHD individuals and gastrointestinal symptoms are closely associated, the microbiota in the stool might be different from normal children without ADHD.
Accumulating evidence implicated gut microbiota play a role in autism spectrum disorder (ASD). A huge community of microorganisms in the gastrointestinal (GI) tract impacts the development and function of the immune, metabolic, and nervous systems via the gut-brain axis. Majority of studies shown the diversity of gut microbiota changed in children with ASD compared with that of typically developing (TD) children, suggesting that the overall microbiota composition altered in ASD. Differences were observed between ASD and TD when comparing the abundance of bacteria in phyla and species level. Potential faecal bacteria biomarkers in the stool of children with ASD will be a useful non-invasive tool for early detection that will benefit more children with suspected conditions.
The microbiota was involved in many aspects of behaviour was confirmed in animal studies and human trial but it remains unclear whether gut microbiota recover in children with ASD after the intervention. Genetic research has revealed that if a child has a sibling with ADHD, the risk of developing ADHD is three to four times higher than that of children with siblings without ADHD.
Besides, previous studies showed that maternal unhealthy diet, tobacco use, and the harmful use of alcohol during pregnancy induce a shift in microbial ecology that negatively impacts offspring social behavior and has a fundamental role in the etiopathogenesis of ASD and ADHD. In some cases, children who have experienced stress, emotional abuse and violence are more prone to ADHD behaviour.
- Medical subject headings
- Autistic Disorder, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| ASD and/or ADHD children (Case group) | Suspected or confirmed cases of ASD and/or ADHD children (Case group); no intervention(s) to be administered. | |
| Parent group | Parents of suspected or confirmed cases of ASD and/or ADHD children; no intervention(s) to be administered. | |
| Sibling group | Typically developed siblings of suspected or confirmed cases of ASD and/or ADHD children; no intervention(s) to be administered. | |
| Control group | Typically developed children not related to the case group ; no intervention(s) to be administered. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify the microbial species in stool in suspected and confirmed ASD and/or ADHD children
Random Forest (RF) will be used for identifying the species of the biomarkers. The importance value of each species to the classification model will be evaluated by recursive feature elimination.
Measured: 6 months
Secondary outcomes (5)
To confirm different microbial species in stool in suspected and confirmed ASD and/or ADHD children across 2 years
Different species will be compared in terms of binary classifiers with Area Under the Curve (AUC) in Receiver Operating Characteristic (ROC) curves.
Measured: 2 years
To confirm different microbial species in stool at different age groups in suspected and confirmed ADS and/or ADHD children across 2 years
Different species will be compared in terms of binary classifiers with Area Under the Curve (AUC) in Receiver Operating Characteristic (ROC) curves.
Measured: 2 years
To correlate the changes in microbial species in stool with different diet habits in ASD and/or ADHD children across 2 years
Correlation statistical method will be used
Measured: 2 years
To correlate the changes in microbial species in stool between the suspected and confirmed ASD and/or ADHD children with their siblings, parent or typically developed children at baseline
Correlation statistical method will be used
Measured: baseline
To correlate the changes in microbial species in stool with different food additives levels in all subject groups at baseline
Correlation statistical method will be used
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start15 May 2021
- Primary completion14 May 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AutismStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siew Chien NG, Chinese University of Hong Kong
- Investigators
- Siew Ng, PhD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04890717
- Sponsor's protocol ID
- Mic_ASDADHD
- Status last verified
- Feb 2023
- First submitted
- 9 May 2021
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbial Stool Biomarkers for Prediction of Autism and ADHD in Children
- ClinicalTrials.gov ID
- NCT04890717
- Acronym / sponsor ID
- Mic_ASDADHD
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 15 May 2021 (actual)
- Primary completion
- 14 May 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 18 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autism (ASD) is one of the frequent neurodevelopmental disorders that children would occur. Many studies have shown that individuals with Autism are more common to experience significant gastrointestinal problems than other individuals. Symptoms include constipation, diarrhea, abdominal pain and gastric reflux. A recent study with 50 children with ASD, 50 children with other developmental disabilities and 50 healthy control children, it found that 70% of ASD children had presented with GI symptoms, compared with 42% of developmental disabilities children and 28% of developing children, it is believed that ASD children will have a distinctive microbial pattern in the stool.
Attention-deficit/hyperactivity disorder (ADHD) is another neurodevelopmental and neurobehavioral disorder. A study found that ADHD individuals experience significantly higher rate of stomach pain and bowel problems than other control individuals. It is suggested that the microbiota in the stool of ADHD children might be different. Genetic study also found that if a child has a sibling with ADHD, the risk of developing ADHD is three to four times higher than that of children with siblings without ADHD.
Detailed description
Autism Spectrum Disorder (ASD) was first developed by Kanner in 1943. In Hong Kong, a study showed that as many as 49 out of 10,000 children were diagnosed in Autism. ASD is one of the frequent neurodevelopmental disorders that children would occur. Many studies have shown that individuals with Autism are more common to experience significant gastrointestinal problems than other individuals. Symptoms include constipation, diarrhoea, abdominal pain and gastric reflux. In a study with 160 children with ASD, 59% had GI symptoms, including diarrhoea, unformed stool, constipation, bloating and gastroesophageal reflux (GERD). A study compared 51 ASD children, and 40 healthy control children found that 63% of ASD children had moderate or severe diarrhoea and constipation symptoms. In contrast, only 2% of control children had such experience. Similarly, a study of 150 children, with 50 children with ASD, 50 children with other developmental disabilities and 50 healthy control children, it found that 70% of ASD children had presented with GI symptoms, compared with 42% of developmental disabilities children and 28% of developing children. Other study stated that such untreated GI symptoms might worsen the behavioural issue of ASD children. As there is a strong relationship between ASD children and GI symptoms, it is believed that ASD children will have a distinctive microbial pattern in the stool.
Attention-deficit/hyperactivity disorder (ADHD) is another neurodevelopmental and neurobehavioral disorder. In Hong Kong, there were 8.9% of ADHD children among Primary one Chinese schoolboys. A large study (N=6483) found that ADHD individuals experience a significantly higher rate of stomach pain and bowel problems than other control individuals. McKeown did another study also reported that ADHD children were more likely to experience constipation and stool incontinence than normal healthy children. In one study that compared the Gastrointestinal Severity Index scoring between children with ADHD and healthy subjects, children with ADHD had significantly higher mean and scored higher in constipation, diarrhoea and flatulence variables. As the findings of ADHD individuals and gastrointestinal symptoms are closely associated, the microbiota in the stool might be different from normal children without ADHD.
Accumulating evidence implicated gut microbiota play a role in autism spectrum disorder (ASD). A huge community of microorganisms in the gastrointestinal (GI) tract impacts the development and function of the immune, metabolic, and nervous systems via the gut-brain axis. Majority of studies shown the diversity of gut microbiota changed in children with ASD compared with that of typically developing (TD) children, suggesting that the overall microbiota composition altered in ASD. Differences were observed between ASD and TD when comparing the abundance of bacteria in phyla and species level. Potential faecal bacteria biomarkers in the stool of children with ASD will be a useful non-invasive tool for early detection that will benefit more children with suspected conditions.
The microbiota was involved in many aspects of behaviour was confirmed in animal studies and human trial but it remains unclear whether gut microbiota recover in children with ASD after the intervention. Genetic research has revealed that if a child has a sibling with ADHD, the risk of developing ADHD is three to four times higher than that of children with siblings without ADHD.
Besides, previous studies showed that maternal unhealthy diet, tobacco use, and the harmful use of alcohol during pregnancy induce a shift in microbial ecology that negatively impacts offspring social behavior and has a fundamental role in the etiopathogenesis of ASD and ADHD. In some cases, children who have experienced stress, emotional abuse and violence are more prone to ADHD behaviour.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ASD and/or ADHD children (Case group) | – | –Suspected or confirmed cases of ASD and/or ADHD children (Case group); no intervention(s) to be administered. |
| Parent group | – | –Parents of suspected or confirmed cases of ASD and/or ADHD children; no intervention(s) to be administered. |
| Sibling group | – | –Typically developed siblings of suspected or confirmed cases of ASD and/or ADHD children; no intervention(s) to be administered. |
| Control group | – | –Typically developed children not related to the case group ; no intervention(s) to be administered. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Subjects include * suspected or confirmed cases of ASD and/or ADHD children (Case group), * typically developed siblings of suspected or confirmed cases of ASD and/or ADHD children (Sibling group), * parents of suspected or confirmed cases of ASD and/or ADHD children (Parent group) * typically developed children not related to the case group (Control Group).
Key inclusion criteria (8 listed)
- Children aged under 18 years old; and
- The parents or legal guardian agree to hand in the stool samples of children; and agree to complete questionnaires; and
- The parents or legal guardian agree to sign the informed consent form for the children
- Their suspected or confirmed ASD or ADHD children participated in the study; and
- Agree to hand in stool samples and complete questionnaires; and
Key exclusion criteria (3 listed)
- Any subject taken probiotics, prebiotics, antibiotics 30 days before enrollment.
- Subjects can be re-approached or join the study 30 days after taking probiotics, prebiotics, antibiotics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To identify the microbial species in stool in suspected and confirmed ASD and/or ADHD children
Time frame: 6 months
Random Forest (RF) will be used for identifying the species of the biomarkers. The importance value of each species to the classification model will be evaluated by recursive feature elimination.
5 secondary outcomes
To confirm different microbial species in stool in suspected and confirmed ASD and/or ADHD children across 2 years
Time frame: 2 years
To confirm different microbial species in stool at different age groups in suspected and confirmed ADS and/or ADHD children across 2 years
Time frame: 2 years
To correlate the changes in microbial species in stool with different diet habits in ASD and/or ADHD children across 2 years
Time frame: 2 years
To correlate the changes in microbial species in stool between the suspected and confirmed ASD and/or ADHD children with their siblings, parent or typically developed children at baseline
Time frame: baseline
To correlate the changes in microbial species in stool with different food additives levels in all subject groups at baseline
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Siew Ng, PhD principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autism and ADHD, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Terence Yeung, Bsc (26373225, wanchunyeung@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify the microbial species in stool in suspected and confirmed ASD and/or ADHD children (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.