Microbiota Transfer Therapy for Adults With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders (MTT-ASD)

This is a clinical trial of Microbiota Transplant Therapy (MTT) for adults with autism spectrum disorders (ASD) who have gastrointestinal problems.

Previous research has shown that individuals with ASD have a low diversity of gut bacteria, and low diversity is generally associated with poor gastrointestinal (GI) health. We previously found that MTT therapy for children with ASD and GI symptoms was helpful in reducing their GI symptoms, reducing their ASD symptoms, and increasing their diversity of gut bacteria.

This clinical trial will investigate the hypothesis that MTT therapy will be helpful for adults with ASD who have GI symptoms.

Study Overview

• Status: Active, not recruiting
• Conditions: Autism Spectrum Disorder; Gastrointestinal Disorder
• Intervention / Treatment: Drug: Vancomycin; Drug: MoviPrep; Biological: Full Spectrum Microbiota

Detailed Description

For adults ages 18-60 years with ASD and gastrointestinal problems, the investigators propose a Phase 2 clinical trial to evaluate the safety and efficacy of MTT. The study will also determine if longer treatment is beneficial, and to conduct a longer observation after treatment stops to determine long-term safety and efficacy. The three parts of this trial are described below.

Part 1: Placebo-Controlled Treatment The trial will begin with a randomized, double-blind, placebo-controlled trial which will include a 2-week treatment with oral vancomycin (or placebo), then 1 day of Moviprep to cleanse the bowel of vancomycin and bacteria/feces (all participants, since its bowel-emptying effect cannot be blinded), followed by oral administration of Full Spectrum Microbiota (FSM) or placebo. An initial high dose of FSM (or placebo) for two days will be followed by a lower maintenance dose of FSM (or placebo) for 8 weeks.

Part 2 Extension and Cross-Over

• For the treatment group from Part 1, there will be an 8-week extension of the maintenance dose, to determine if longer treatment has additional benefits.
• For the placebo group from Part 1, they will receive MoviPrep, an initial high dose of FSM for 2 days, and then a lower dose of FSM for 8 weeks (similar to the treatment group in Part 1, but without the vancomycin). This will help us determine if pre-treatment with vancomycin is needed or not.

Part 3: Follow-up There will be follow-up evaluations at 6, 12, and 18 months after treatment is stopped, to assess long-term efficacy and possible adverse effects.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85287
      • Arizona State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult aged 18-60 years
2. Diagnosis of autism per both the Autism Diagnostic Interview - Revised (ADI-R) and the Childhood Autism Rating Scale 2 (CARS-2).
3. GI disorder as defined below that has lasted for at least 3 years.
4. No changes in medications, supplements, diet, therapies, or education in last 3 months, and no intention to change them during the clinical trial.
5. General good physical health aside from gastrointestinal problems
6. Neurotypical adult observer (such as parent, guardian, or sibling) who observes adult for at least 4 hours/week who can serve as an Evaluator to complete questionnaires on their symptoms with the assistance of the Participant as much as they are able.
7. Ability to swallow pills (without chewing)

Exclusion Criteria:

1. Antibiotics in last 3 months
2. Probiotics in last 2 months, or fecal transplant in last 12 months
3. Single-gene disorder (Fragile X, etc.)
4. Major brain malformation
5. Tube feeding
6. Severe gastrointestinal problems that require immediate treatment (life-threatening)
7. Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions
8. Severely underweight/malnourished
9. Recent or scheduled surgeries
10. Current participation in other clinical trials
11. Females who are pregnant or who are sexually active without effective birth control. We will conduct a urine pregnancy test on all female participants as part of the screening and at each clinical visit.
12. Allergy or intolerance to vancomycin or MoviPrep

13. Clinically significant abnormalities at baseline on two blood safety tests: Comprehensive Metabolic Panel and Complete Blood Count with Differential.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A receives treatment in Part 1 and Part 2	Drug: Vancomycin; Oral vancomycin is administered to reduce pathogenic bacteria.; Drug: MoviPrep; MoviPrep is given at the end of vancomycin therapy to remove the vancomycin and remaining bacteria prior to administering Full-Spectrum Microbiota; Biological: Full Spectrum Microbiota; Gut bacteria from healthy human donors are administered orally in a pill form; Other Names: fecal microbiota transplant
Other: Group B; Group B receives no treatment in Part 1, but does receive treatment in Part 2	Drug: MoviPrep; MoviPrep is given at the end of vancomycin therapy to remove the vancomycin and remaining bacteria prior to administering Full-Spectrum Microbiota; Biological: Full Spectrum Microbiota; Gut bacteria from healthy human donors are administered orally in a pill form; Other Names: fecal microbiota transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Childhood Autism Rating Scale (CARS) from baseline to 10 weeks	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.	baseline; month 2.5, 4.5, 10.5, 16.5, 22.5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Daily Stool Log (DSL) from baseline to 10 weeks	The DSL is a report of the number and type of stools over 14 days. Each stool is rated on a scale of 1-7, where 1=very hard, 4=normal, 7=very soft/liquid. The DSL is scored by the number of days of an abnormal stool (type 1-2 or 6-7) or no stool.	baseline for 2 weeks; daily for 18 weeks, and 2 weeks at month 10, 16, 22
Change in Social Responsiveness Scale - 2 from baseline to 10 weeks 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.	baseline; weeks 2, 4, 6, 8, 10, 12, 14, 16, 18; months 10.5, 16.5, 22.5
Change in Aberrant Behavior Checklist from baseline to 10 weeks	a questionnaire about aberrant behaviors. Scores range from 0 to 174, with higher scores indicating more severe behaviors	baseline; month 2.5, 4.5, 10.5, 16.5, 22.5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gastrointestinal Stool and Symptom Questionnaire for Autism, from baseline to 10 weeks	a questionnaire about GI-related symptoms.	baseline; weeks 2, 4, 6, 8, 10, 12, 14, 16, 18; month 10.5, 16.5, 22.5
Change in Microbiome composition from baseline to 10 weeks	analysis of the bacterial composition of stool samples, at the species, genus, and phylum level	baseline; month 1, 2.5, 3.5, 4.5, 10.5, 16.5, 22.5
Change in the Vineland Adaptive Behavior Scale - II, from baseline to 10 weeks	questionnaire about adaptive behaviors; it yields the developmental age of the participant	baseline; month 2.5, 4.5, 22.5
Change in Ohio State University Clinical Impressions Scale, from baseline 10 weeks	assessment of autism symptoms by a clinician. It rates 10 symptoms on a scale of 1-7, with higher scores indicating worse symptoms.	baseline; month 2.5, 4.5
Change in Parent Global Impressions, from baseline to 10 weeks	Assessment of autism symptoms. It rates 20 symptoms on a scale of 1-7, with higher scores indicating worse symptoms	baseline; weeks 2, 4, 6, 8, 10, 12, 14, 16, 18; month 10.5, 16.5, 22.5

Collaborators and Investigators

• Sponsor: Arizona State University
• Investigators: Study Director: James B Adams, PhD, Arizona State University

Publications and helpful links

General Publications

• Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.

Helpful Links

• link to more information about the research group

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2018
• Primary Completion (Actual): April 15, 2022
• Study Completion (Anticipated): December 15, 2024

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: vancomycin; fecal transplant; fecal microbiota transplant; microbiota transplant; moviprep
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Gastrointestinal Diseases; Digestive System Diseases; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: MTT-Adults-1; Wi1XWH-16-1-0492 (Other Grant/Funding Number: Department of Defense)

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: Yes
• Studies a U.S. FDA-regulated device product: No