MTT for Children With ASD Who Have Gastrointestinal Disorders

Sponsor

Arizona State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04182633

Collaborator

Arizona State University Foundation (Other), University of Minnesota (Other), Finch Therapeutics (Other)

Enrollment

Location

Arms

61.5

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators propose to investigate Microbiota Transfer Therapy (MTT) for treating children with Autism Spectrum Disorder (ASD) and gastrointestinal problems (primarily constipation and/or diarrhea). MTT involves a combination of 10 days of oral vancomycin (an antibiotic to kill pathogenic bacteria), followed by a bowel cleanse, followed by 12 weeks of Fecal Microbiota (FM).

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder Gastro-Intestinal Disorder Constipation Diarrhea	Combination Product: vancomycin, Miralax, intestinal microbiota Combination Product: placebo vancomycin, Miralax, placebo intestinal microbiota	Phase 2

Detailed Description

For children ages 5-17 years with Autism Spectrum Disorder and gastrointestinal problems, a Phase 2 clinical trial will evaluate the safety, tolerability, and efficacy of MTT. The three parts of this trial are described below.

Part 1: Randomized Trial The trial will begin with a randomized, double-blind, placebo-controlled trial which will include a 2-week treatment with oral vancomycin (Group A) or placebo (Group B), then 1 day of Miralax to cleanse the bowel of vancomycin and bacteria/feces (both groups), followed by oral administration of FM (Group A) or placebo (Group B). An initial high dose of FM (or placebo) for two days will be followed by a lower maintenance dose of FM or placebo for 12 weeks.

Part 2: Extension (Group A) and Treatment (Group B)

For Group A there will be 12-week observation period
For Group B, there will be treatment similar to that received by the treatment group in Part 1 (partial cross-over, open-label), except that they will not receive vancomycin. So, they will be treated with Miralax followed by an initial high dose of FM for 2 days, and then a maintenance dose of FM for 12 weeks. The purpose of this arm is to determine if vancomycin is necessary or not.

Part 3: Follow-up There will be a follow-up evaluation at 6, 12, and 18 months after treatment ends, to determine long-term safety and efficacy.

Participant duration will be approximately 6.5 months for treatment, and follow-up at 6, 12 and 18 months after treatment ends.

Study duration will be approximately 4 years, including IRB approvals, training staff, recruiting, clinical trial, data analysis, and reporting.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, double-blind, placebo-controlled study.This is a randomized, double-blind, placebo-controlled study.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Randomized, double-blind, placebo-controlled study.

Primary Purpose:

Treatment

Official Title:

Microbiota Transfer Therapy for Children With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders

Actual Study Start Date :

Nov 15, 2019

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A - Treatment Group This group will receive vancomycin for 14 days, then Miralax for 1 day, then intestinal microbiota for 2 days at high dose, then intestinal microbiota for 12 weeks at a maintenance dose	Combination Product: vancomycin, Miralax, intestinal microbiota vancomycin for 14 days, then Miralax for 1 day, then intestinal microbiota (high dose for 2 days, then maintenance dose for 12 weeks)
Placebo Comparator: Group B - Control Group (Miralax only for 1 day) This group will receive placebo vancomycin for 14 days, then Miralax for 1 day, then placebo intestinal microbiota for 2 days at high dose, then placebo intestinal microbiota for 12 weeks at a maintenance dose	Combination Product: placebo vancomycin, Miralax, placebo intestinal microbiota placebo vancomycin for 14 days, then Miralax for 1 day, then placebo intestinal microbiota (high dose for 2 days, then maintenance dose for 12 weeks)

Arm

Intervention/Treatment

Experimental: Group A - Treatment Group

This group will receive vancomycin for 14 days, then Miralax for 1 day, then intestinal microbiota for 2 days at high dose, then intestinal microbiota for 12 weeks at a maintenance dose

Combination Product: vancomycin, Miralax, intestinal microbiota

vancomycin for 14 days, then Miralax for 1 day, then intestinal microbiota (high dose for 2 days, then maintenance dose for 12 weeks)

Placebo Comparator: Group B - Control Group (Miralax only for 1 day)

This group will receive placebo vancomycin for 14 days, then Miralax for 1 day, then placebo intestinal microbiota for 2 days at high dose, then placebo intestinal microbiota for 12 weeks at a maintenance dose

Combination Product: placebo vancomycin, Miralax, placebo intestinal microbiota

placebo vancomycin for 14 days, then Miralax for 1 day, then placebo intestinal microbiota (high dose for 2 days, then maintenance dose for 12 weeks)

Outcome Measures

Primary Outcome Measures

Childhood Autism Rating Scale (CARS) [change in score from baseline to 14 weeks (end of treatment)]
An evaluation by a trained evaluator of autism symptoms. The range is 15-60, and scores in the range of 27-30 or higher are indicative of autism.
Gastrointestinal Symptom Severity Scale (GSRS) [change in score from baseline to 14 weeks (end of treatment)]
A 15-item questionnaire for evaluation of GI symptoms, with each item rated on a scale of 1 (no symptoms) to 7 (severe symptoms), with an average score of 1-7.

Secondary Outcome Measures

Daily Stool Record [change in % abnormal days from baseline (for 2 weeks) vs. week 14 (2 weeks from week 13-14)]]
The DSR is a daily record of bowel movements including Bristol Stool Form scale. It is rated as the % of days with an abnormal report (abnormal stool, no stool, or the use of a gastrointestinal treatment). A higher percentage indicates worse symptoms.
Social Responsiveness Scale 2 [change in score from baseline to 14 weeks (end of treatment)]
A questionnaire about social skills, where higher scores suggest more severe autism. Scores range from 0 to 195, with higher scores indicating more severe problems.
Aberrant Behavior Checklist [change in score from baseline to 14 weeks (end of treatment)]
A questionnaire about aberrant behaviors. Scores range from 0 to 174, with higher scores indicating more severe behaviors

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria for Children with ASD

Child aged 5-17 years
Diagnosis of autism per the Childhood Autism Rating Scale 2 (CARS-2) and either the Autism Diagnostic Interview-Revised (ADI-R) or the Autism Diagnostic Observation Schedule 2 (ADOS 2).
GI disorder as defined below that has lasted for at least 3 years.
No changes in medications, supplements, diet, therapies, or education in last 3 months, and no intention to change them during the clinical trial.
General good physical health aside from gastrointestinal problems
Ability to swallow pills (without chewing)

Exclusion Criteria for Children with ASD

Antibiotics in last 3 months (does not apply to topical antibiotics)
Probiotics in last 2 months, or fecal transplant in last 12 months
Single-gene disorder (Fragile X, etc.)
Major brain malformation
Tube feeding
Severe gastrointestinal problems that require immediate treatment (life-threatening)
Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions
Severely underweight/malnourished (per physician clinical judgement)
Unstable, poor health; seizure disorder that is not responsive to treatment or not on stable management or complex type; or other health conditions that would significantly increase their risk of adverse effects (per physician clinical judgement)
Recent or scheduled surgeries
Current participation in other clinical trials
Females who are pregnant or who are sexually active without effective birth control.
Allergy or intolerance to vancomycin or Miralax
Clinically significant abnormalities at baseline on two blood safety tests: Comprehensive Metabolic Panel and Complete Blood Count with Differential.
Psychotropic medication daily use - Current or within past 2 months - which are known to interfere in gastrointestinal function
Evidence of significant impairment of immune system, or taking medications that can compromise the immune system, and thus increase risk if exposed to multiple-drug resistant bacteria.