Children With AutismNCT04246398
FMT in Children With Autism and Gastrointestinal Symptoms
A study testing FMT in people with Children With Autism, run by Assaf Harofeh MC at 1 site in Israel.
Trial summary
1. ASD children with gastrointestinal problems that interfere with daily routine will be recruited at the center for Autism led by Prof Zachor, and at the Pediatric Neurology \& Development Center at Shamir Medical Center. Publications in the social media- facebook and support groups for Autism will also be used. Read more about this study
- Who is it for?
- Ages 7 to 20 years
- Conditions the study is for
- Children With Autism
- What is being tested?
- FMT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- Feb 2020to Dec 2022
- Phase
- Interventional
- 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 7 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- ASD Boys or girls 7 - 20 years of age
- suffering gastro-intestinal symptoms and/or food selectivity that interfere with daily routine
- Patients not started on immune-suppressive or anti-inflammatory medications.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of childbearing potential will have a urine pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT.
- Hasn't taken antibiotics 2 days prior to 1st visit.
- Ability of parents or other legal guardian to understand and the willingness to sign a written informed consent document, including the willingness to accept risk of unrelated donor stool.
- Ability to swallow oral medications.
Who cannot join
- Severe GI problems that require immediate treatment (life-threatening).
- recent/scheduled surgeries
- diagnosed as severely malnourished or underweight
- diagnosed with a single-gene disorder
- major brain malformations
- inflammatory bowel diseases
Show all 14Show fewer
- known positive serology for celiac disease or eosinophilic esophagitis
- Pregnancy / breast-feeding
- Using immune-suppressive or anti-inflammatory medications
- Active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Delayed gastric emptying syndrome
- Known chronic aspiration
- History of significant allergy to foods
- Unable to swallow pills
Trial locations and contacts
1 site in 1 country.
About this study
- ASD children with gastrointestinal problems that interfere with daily routine will be recruited at the center for Autism led by Prof Zachor, and at the Pediatric Neurology \& Development Center at Shamir Medical Center. Publications in the social media- facebook and support groups for Autism will also be used. The decision whether or not to initiate any medical treatment will not be influenced by the study investigators and will be made solely by the treating doctor.
- If possible, participants will provide informed consent after receiving a thorough explanation by the study team, as will both parents or other legal guardians.
- Two groups randomization will be performed, group A and group B. The group randomization will be double blinded.
- Participants randomized to group A will receive 10 capsules FMT twice a week for 3 weeks, and at week 12 followed by 3 weeks placebo twice a week.
- Participants randomized to group B will receive 10 capsules placebo twice a week for 3 weeks and at week 12 followed by 3 weeks FMT twice a week.
- At baseline, participants will undergo a full physical examination, vital signs, medical questionnaire, ROME III questionnaire for kids >age4 />age 10, ATN-GISSI-17 questionnaire, Aut-Eat questionnaire regarding eating habbits, the Social Responsiveness Scale (SRS) and the Adaptive Behavior Assessment System (ABAS).
- Parents/ care providers will fill a daily symptoms follow-up questionnaire at baseline
- Fecal samples will be provided for analysis of microbiome and proteome at beseline, weeks 3,12, 15 and 6+9 months.
- At each FMT/Placebo administration a short questionnaire asking about possible adverse events, GI symptoms, overall well-being, and medication changes will be administered
Read the detailed description
About 50% of children with Autism spectrum disorder (ASD) tend to suffer from one or more gastrointestinal (GI) symptoms.The GI symptoms vary from constipation (~20%), diarrhea (~14%), Abdominal pain/discomfort (14%), bloating (12%), incontinence (12%), reflux (7.4%), nausia (6%) and difficult with bowel movements (6%).
The severity of ASD is associated with the observed GI symptoms, although no cause-effect relationship between GI symptoms and ASD was proven so far. ASD with GI symptoms patients might display significant behavioral manifestations, such as anxiety, self-injury and aggression and these may be attributed to the GI symptoms themselves. Therefore alleviation of the GI symptoms could be important also for improvement of ASD.
In addition to the possibility that the nervous system influences the gut and the GI symptoms, there is also the possibility that the gut and the microbiome within the gut may influence the central nervous system.
Considering the findings that children with ASD have a history of using significantly more antibiotics and that gut permeability increases in ASD it is reasonable to assume that ASD patients have distinct microbiomes and gut metabolites.
Nevertheless, perhaps changing the gut microbiome could lead to improvement in some of the symptoms. So far, studies on influencing ASD (behavior and GI symptoms) by addressing the gut microbiome are optimistic but mostly open-labeled and still inconclusive.
- Conditions
- Children With Autism
- Being tested
- FMT, FMT - placebo
- Keywords
- Fecal microbiota transplant, autism spectrum disorder, children
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMTOther
Also called Fecal microbiota transplant
Participants will be asked to fast for 4 hours prior to and 1 hour following capsule intake.
Each capsule will be taken with a sip of water, Capsules must not be crushed, chewed, or dissolved Participants will be evaluated for 15 minutes immediately following capsule administration.
FMT - placeboOther
Participants will be asked to fast for 4 hours prior to and 1 hour following capsule intake.
Each capsule will be taken with a sip of water, Capsules must not be crushed, chewed, or dissolved Participants will be evaluated for 15 minutes immediately following capsule administration.
| Study group | Role | What they receive |
|---|---|---|
| Fecal microbiota transplant (FMT) | Experimental | 10 capsules per dose for 6 consecutive weeks, twice a week, for a total of 120 capsules.
Each inoculum will be prepared from the feces of 1 donor and a dose of 10 capsules contains sieved, concentrated material derived from a mean of 10 grams of fecal matter. Donors are healthy, nonpregnant adults aged 18 to 50 years, taking no medications, and with a normal body mass index (18.5-25 [calculated as weight in kilograms divided by height in meters squared]). Receives: Other: FMT |
| placebo | Placebo comparator | Placebo capsules will consist of a combination of saline/glycerol (same vehicle as FMT capsules). The inner capsules is dark (green colored), so the general appearance of the capsules is the same to the people who do not prepare them. Receives: Other: FMT - placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The safety of using FMT capsules in autistic children with gastrointestinal symptoms is measured by the prevalence and severity of side effects that occurred after taking the capsules, and were documented in a daily follow-up questionnaire
Measured: 3 weeks from the start of the study
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
The safety of using FMT capsules in autistic children with gastrointestinal symptoms is measured by the prevalence and severity of side effects that occurred after taking the capsules, and were documented in a daily follow-up questionnaire
Measured: 15 weeks from the start of the study
Significant change in GI symptoms [efficiency]
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Measured: 3 weeks from the start of the study
Significant change in GI symptoms [efficiency]
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Measured: 15 weeks from the start of the study
Significant change in GI symptoms [efficiency]
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Measured: 6 months from the start of the study
Significant change in GI symptoms [efficiency]
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Measured: 9 months from the start of the study
Secondary outcomes (10)
Change in food selection [efficiency]
The effectiveness of FMT capsules on food selectivity in autistic children is measured using a eating habits questionnaire (Aut-Eat)
Measured: 12 weeks from the start of the study
Change in food selection [efficiency]
The effectiveness of FMT capsules on food selectivity in autistic children is measured using a eating habits questionnaire (Aut-Eat)
Measured: 6 months from the start of the study
Change in food selection [efficiency]
The effectiveness of FMT capsules on food selectivity in autistic children is measured using a eating habits questionnaire (Aut-Eat)
Measured: 9 months from the start of the study
Improving ASD symptoms [efficiency]
The efficacy of FMT capsules in improving ASD symptoms is measured using the SRS questionnaire (Social Responsiveness Scale) The Total Score calculated separately for males and females. It can be expressed as a raw score or a T-score.
Measured: 3 months from the start of the study
Improving ASD symptoms [efficiency]
The efficacy of FMT capsules in improving ASD symptoms is measured using the SRS questionnaire (Social Responsiveness Scale) The Total Score calculated separately for males and females. It can be expressed as a raw score or a T-score.
Measured: 6 months from the start of the study
Diversity and variability of the gut microbiome
Changing the diversity and variability of the gut microbiome measured by sequencing the 16's rRNA.
Measured: 3 weeks from the start of the study
Diversity and variability of the gut microbiome
Changing the diversity and variability of the gut microbiome measured by sequencing the 16's rRNA.
Measured: 12 weeks from the start of the study
Diversity and variability of the gut microbiome
Changing the diversity and variability of the gut microbiome measured by sequencing the 16's rRNA.
Measured: 15 weeks from the start of the study
Diversity and variability of the gut microbiome
Changing the diversity and variability of the gut microbiome measured by sequencing the 16's rRNA.
Measured: 3 months from the start of the study
Diversity and variability of the gut microbiome
Changing the diversity and variability of the gut microbiome measured by sequencing the 16's rRNA.
Measured: 6 months from the start of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2020
- Study startFeb 2020 (estimated)
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Children With AutismStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assaf Harofeh MC
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Assaf Harofeh MC, Assaf-Harofeh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04246398
- Sponsor's protocol ID
- 0052-19-ASF
- Status last verified
- Feb 2020
- First submitted
- 6 Jan 2020
- Last updated
- 5 Feb 2020
- Results posted
- 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 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FMT in Children With Autism and Gastrointestinal Symptoms
- ClinicalTrials.gov ID
- NCT04246398
- Acronym / sponsor ID
- 0052-19-ASF
- Conditions
- Children With Autism
- Keywords
- Fecal microbiota transplant, autism spectrum disorder, children
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assaf Harofeh MCOther government
- Study start
- Feb 2020 (estimated)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 29 Jan 2020 (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.
- ASD children with gastrointestinal problems that interfere with daily routine will be recruited at the center for Autism led by Prof Zachor, and at the Pediatric Neurology \& Development Center at Shamir Medical Center. Publications in the social media- facebook and support groups for Autism will also be used. The decision whether or not to initiate any medical treatment will not be influenced by the study investigators and will be made solely by the treating doctor.
- If possible, participants will provide informed consent after receiving a thorough explanation by the study team, as will both parents or other legal guardians.
- Two groups randomization will be performed, group A and group B. The group randomization will be double blinded.
- Participants randomized to group A will receive 10 capsules FMT twice a week for 3 weeks, and at week 12 followed by 3 weeks placebo twice a week.
- Participants randomized to group B will receive 10 capsules placebo twice a week for 3 weeks and at week 12 followed by 3 weeks FMT twice a week.
- At baseline, participants will undergo a full physical examination, vital signs, medical questionnaire, ROME III questionnaire for kids >age4 />age 10, ATN-GISSI-17 questionnaire, Aut-Eat questionnaire regarding eating habbits, the Social Responsiveness Scale (SRS) and the Adaptive Behavior Assessment System (ABAS).
- Parents/ care providers will fill a daily symptoms follow-up questionnaire at baseline
- Fecal samples will be provided for analysis of microbiome and proteome at beseline, weeks 3,12, 15 and 6+9 months.
- At each FMT/Placebo administration a short questionnaire asking about possible adverse events, GI symptoms, overall well-being, and medication changes will be administered
Detailed description
About 50% of children with Autism spectrum disorder (ASD) tend to suffer from one or more gastrointestinal (GI) symptoms.The GI symptoms vary from constipation (~20%), diarrhea (~14%), Abdominal pain/discomfort (14%), bloating (12%), incontinence (12%), reflux (7.4%), nausia (6%) and difficult with bowel movements (6%).
The severity of ASD is associated with the observed GI symptoms, although no cause-effect relationship between GI symptoms and ASD was proven so far. ASD with GI symptoms patients might display significant behavioral manifestations, such as anxiety, self-injury and aggression and these may be attributed to the GI symptoms themselves. Therefore alleviation of the GI symptoms could be important also for improvement of ASD.
In addition to the possibility that the nervous system influences the gut and the GI symptoms, there is also the possibility that the gut and the microbiome within the gut may influence the central nervous system.
Considering the findings that children with ASD have a history of using significantly more antibiotics and that gut permeability increases in ASD it is reasonable to assume that ASD patients have distinct microbiomes and gut metabolites.
Nevertheless, perhaps changing the gut microbiome could lead to improvement in some of the symptoms. So far, studies on influencing ASD (behavior and GI symptoms) by addressing the gut microbiome are optimistic but mostly open-labeled and still inconclusive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal microbiota transplant (FMT) | Experimental | Other: FMT10 capsules per dose for 6 consecutive weeks, twice a week, for a total of 120 capsules. Each inoculum will be prepared from the feces of 1 donor and a dose of 10 capsules contains sieved, concentrated material derived from a mean of 10 grams of fecal matter. Donors are healthy, nonpregnant adults aged 18 to 50 years, taking no medications, and with a normal body mass index (18.5-25 [calculated as weight in kilograms divided by height in meters squared]). |
| placebo | Placebo comparator | Other: FMT - placeboPlacebo capsules will consist of a combination of saline/glycerol (same vehicle as FMT capsules). The inner capsules is dark (green colored), so the general appearance of the capsules is the same to the people who do not prepare them. |
Who may qualify
- Ages
- 7 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- ASD Boys or girls 7 - 20 years of age
- suffering gastro-intestinal symptoms and/or food selectivity that interfere with daily routine
- Patients not started on immune-suppressive or anti-inflammatory medications.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of childbearing potential will have a urine pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT.
- Hasn't taken antibiotics 2 days prior to 1st visit.
Key exclusion criteria (14 listed)
- Severe GI problems that require immediate treatment (life-threatening).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FMTAlso: Fecal microbiota transplantParticipants will be asked to fast for 4 hours prior to and 1 hour following capsule intake. Each capsule will be taken with a sip of water, Capsules must not be crushed, chewed, or dissolved Participants will be evaluated for 15 minutes immediately following capsule administration. | Other | Fecal microbiota transplant (FMT) |
| FMT - placeboParticipants will be asked to fast for 4 hours prior to and 1 hour following capsule intake. Each capsule will be taken with a sip of water, Capsules must not be crushed, chewed, or dissolved Participants will be evaluated for 15 minutes immediately following capsule administration. | Other | placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 3 weeks from the start of the study
The safety of using FMT capsules in autistic children with gastrointestinal symptoms is measured by the prevalence and severity of side effects that occurred after taking the capsules, and were documented in a daily follow-up questionnaire
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
Time frame: 15 weeks from the start of the study
The safety of using FMT capsules in autistic children with gastrointestinal symptoms is measured by the prevalence and severity of side effects that occurred after taking the capsules, and were documented in a daily follow-up questionnaire
Significant change in GI symptoms [efficiency]
Time frame: 3 weeks from the start of the study
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Significant change in GI symptoms [efficiency]
Time frame: 15 weeks from the start of the study
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Significant change in GI symptoms [efficiency]
Time frame: 6 months from the start of the study
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
Significant change in GI symptoms [efficiency]
Time frame: 9 months from the start of the study
effectiveness of FMT capsules in alleviation of GI symptoms in Autistic children is defined by a significant change in the Rome III questionnaire, used for diagnostic of pediatric functional GI disorders
10 secondary outcomes
Change in food selection [efficiency]
Time frame: 12 weeks from the start of the study
Change in food selection [efficiency]
Time frame: 6 months from the start of the study
Change in food selection [efficiency]
Time frame: 9 months from the start of the study
Improving ASD symptoms [efficiency]
Time frame: 3 months from the start of the study
Improving ASD symptoms [efficiency]
Time frame: 6 months from the start of the study
Diversity and variability of the gut microbiome
Time frame: 3 weeks from the start of the study
Diversity and variability of the gut microbiome
Time frame: 12 weeks from the start of the study
Diversity and variability of the gut microbiome
Time frame: 15 weeks from the start of the study
Diversity and variability of the gut microbiome
Time frame: 3 months from the start of the study
Diversity and variability of the gut microbiome
Time frame: 6 months from the start of the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FMT in people with Children With Autism, run by Assaf Harofeh MC at 1 site in Israel.
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 7 inclusion and 14 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 5 Feb 2020. 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 Israel. 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. Some participants in this study may receive a placebo. 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 Ilan Youngster, M.D (0506301191, youngsteri@shamir.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 3 weeks from the start of the study). The study lists 6 primary outcomes in all. 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 5 Feb 2020.