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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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]). |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FMT | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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 | 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 | 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 | 6 months from the start of the study |
| Significant change in GI symptoms [efficiency] |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 12 weeks from the start of the study |
| Change in food selection [efficiency] |
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Inclusion Criteria:
Exclusion Criteria:
Severe GI problems that require immediate treatment (life-threatening).
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ilan Youngster, M.D | Contact | 0506301191 | youngsteri@shamir.gov.il |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Assaf-HarofehMC | Ẕerifin | 70300 | Israel |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| FMT - placebo | Other | 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. |
|
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 |
| 9 months from the start of the study |
The effectiveness of FMT capsules on food selectivity in autistic children is measured using a eating habits questionnaire (Aut-Eat)
| 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) | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 6 months from the start of the study |