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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Autism Spectrum Disorder, Gastrointestinal Disorder

Intervention / Treatment
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* Drug: Vancomycin
* Drug: MoviPrep
* Biological: Full Spectrum Microbiota


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged 18-60 years Diagnosis of autism per both the Autism Diagnostic Interview - Revised (ADI-R) and the Childhood Autism Rating Scale 2 (CARS-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 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. Ability to swallow pills (without chewing) Exclusion Criteria: Antibiotics in last 3 months 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 Recent or scheduled surgeries Current participation in other clinical trials 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. Allergy or intolerance to vancomycin or MoviPrep Clinically significant abnormalities at baseline on two blood safety tests: Comprehensive Metabolic Panel and Complete Blood Count with Differential. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are two groups. In Part 1, group A receives treatment and group B receives placebo. In Part 2, group A continues to receive treatment, and group B is switched to treatment.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fecal transplant, fecal microbiota transplant, microbiota transplant, vancomycin, moviprep