FMT in Children With Autism and Gastrointestinal Symptoms

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. 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.
2. If possible, participants will provide informed consent after receiving a thorough explanation by the study team, as will both parents or other legal guardians.
3. Two groups randomization will be performed, group A and group B. The group randomization will be double blinded.
4. 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.
5. 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.
6. 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).
7. Parents/ care providers will fill a daily symptoms follow-up questionnaire at baseline
8. Fecal samples will be provided for analysis of microbiome and proteome at beseline, weeks 3,12, 15 and 6+9 months.
9. At each FMT/Placebo administration a short questionnaire asking about possible adverse events, GI symptoms, overall well-being, and medication changes will be administered

Study Overview

• Status: Unknown
• Conditions: Children With Autism
• Intervention / Treatment: Other: FMT; Other: FMT - placebo

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ilan Youngster, M.D; Phone Number: 0506301191; Email: youngsteri@shamir.gov.il

Study Locations

• Israel
  • Zerifin, Israel, 70300
    • Assaf-HarofehMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal microbiota transplant (FMT); 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]).	Other: FMT; 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.; Other Names: Fecal microbiota transplant
Placebo Comparator: placebo; 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.	Other: FMT - placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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]	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

Secondary Outcome Measures

Outcome Measure	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]	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

Collaborators and Investigators

• Sponsor: Assaf Harofeh MC

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 2, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: children; autism spectrum disorder; Fecal microbiota transplant
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: 0052-19-ASF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No