The investigators propose to investigate Microbiota Transfer Therapy (MTT) for treating patients with Autism-spectrum disorder with Gastrointestinal disorders (constipation, diarrhea, and/or abdominal pain). MTT involves a combination of 14 days of oral vancomycin (an antibiotic to kill pathogenic bacteria), followed by 1 day of bowel cleanse using Miralax, followed by 5 days of high dose MTP-101P with an antacid, followed by 12 weeks of a lower maintenance dose of MTP-101P with an antacid.
For children 4 to less than \<18 years old with Autism-spectrum disorder with Gastrointestinal disorders (constipation, diarrhea, and/or abdominal pain). This will be a Phase 2 randomized controlled trial to compare two dosing strategies for microbiota transplant vs. placebo. Participants will be randomly assigned to Group A, B, C or D Part 1: Placebo-Controlled Treatment (15 Weeks) The trial will begin with a randomized, double-blind, placebo-controlled trial which will include a 14-day treatment with oral vancomycin (or placebo), then 1 day of Miralax to cleanse the bowel of vancomycin and bacteria/feces (all participants, since its bowel-emptying effect cannot be blinded), followed by 5 days of initial high dose of MTP-101P taken daily 5 minutes after antacid, and then 12 weeks of a lower maintenance dose of MTP-101P taken daily 5 minutes after an antacid. Group A: Real Treatment. Dose 1 Group B: Real Treatment. Dose 2 Group C: Placebo vancomycin, real Miralax, placebo MTP-101P, real antacid. Group D: Placebo vancomycin, real Miralax, placebo MTP-101P, real antacid. Part 2: Open-Label Observation and Cross-Over (12 weeks) Group A: Observation over the next 12 weeks (no additional treatment). Group B: Observation over the next 12 weeks (no additional treatment). Group A and B completes study at end of part 2. Group C will receive the same dosage group A received in part 1 (Dose 1). This includes 14 days of vancomycin, Miralax, and an initial high dose of MTP-101P for 5 days taken daily 5 minutes after an antacid, and then a lower dose of MTP-101P for 12 weeks taken daily 5 minutes after antacid. Group D will receive the same dosage group B received in part 1 (Dose 2). This includes 14 days of vancomycin, Miralax, and an initial high dose of MTP-101P for 5 days taken daily 5 minutes after an antacid, and then a lower dose of MTP-101P for 12 weeks taken daily 5 minutes after antacid. Part 3: Follow Up Group C and D. There will be a follow-up evaluation 15 weeks post-treatment after the end of Part 2, to assess long-term efficacy and possible adverse effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
MTP-101P is comprised of standardized dose of total fecal microbiota purified from the stool of healthy donors. Donors are carefully screened via health status questionnaires, physical examinations, reviews of comprehensive medical history, clinical laboratory evaluations, serologic and genomic tests for infectious diseases and metabolic health, and stool-related pathogen testing. The material from the donors is purified to remove the majority of non-bacterial material, washed, lyophilized, and provided to the patient in a sachet contained within a mixing bottle.
Oral vancomycin is an antibiotic used for treating C. difficile-associated diarrhea and staphylococcal-induced enterocolitis. Duration: 14 Days
Miralax is a common over-the-counter laxative and bowel cleanse
The antacid will be aluminum/magnesium hydroxide, 1x/day, 5 minutes before the MTP-101P. Each 5 ml consists of Aluminum Hydroxide - 200 mg, Magnesium Hydroxide - 200 mg, and Simethicone - 20 mg. If some participants cannot tolerate the aluminum/magnesium hydroxide, we will allow calcium carbonate alternatives equivalent in acid neutralizing capacity. Duration: 12 weeks
The same packaging will be used as for MTP-101P, but the sachets will contain a freeze-dried mixture of normal saline containing 10% Trehalose. Duration: 12 weeks
Same packaging and liquid carrier and flavoring used as for the oral vancomycin, but no vancomycin. Duration: 14 days
Autism/Asperger's Research Group at Arizona State University
Tempe, Arizona, United States
Childhood Autism Rating Scale (CARS-2)
A 15-item scale that can be used to both diagnose autism and ASD and to assess the overall severity of symptoms
Time frame: Baseline (0-30 days prior to treatment) vs End of Treatment (Day 104)
Daily Stool Record (DSR)
Participants will report the number of abnormal events during a 14 day period. An event includes no bowel movement during 1 day, unusually hard stool (Bristol Stool Form type 1-2), unusually soft stool (Bristol Stool Form type 6-7), four or more bowel movements in 1 day, abdominal pain, or use of GI medication. The units are number of events regardless of type of event.
Time frame: Screening (0-120 days prior to Baseline) vs Baseline (0-30 days prior to treatment) vs End of Treatment (Day 104)
Gastrointestinal Symptom Rating Scale (GSRS)
An assessment of GI symptoms based on 15 questions, which are then scored in five domains (abdominal pain, reflux, indigestion, diarrhea, and constipation). Symptoms are rated on a 7-point Likert scale including no discomfort at all (1), slight discomfort (2), mild discomfort (3), moderate discomfort (4), moderately severe discomfort (5), severe discomfort (6), and very severe discomfort (7).
Time frame: Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104
Clinical Global Impression - Gastrointestinal (CGI-GI)
This assessment is conducted by the study physician and assess the severity of GI symptoms on a 7-point scale. The severity scale rates the severity of the patient's illness including normal, not at all ill (1), borderline mentally ill (2), mildly ill (3), moderately ill (4), markedly ill (5), severely ill (6), among the most extremely ill patients (7).
Time frame: Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)
Clinical Global Impression - Autism (CGI-A)
This assessment is conducted by the study physician and assess the severity of Autism Symptoms on a 7-point scale. The severity scale rates the severity of the patient's illness including normal, not at all ill (1), borderline mentally ill (2), mildly ill (3), moderately ill (4), markedly ill (5), severely ill (6), among the most extremely ill patients (7).
Time frame: Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)
National Survey on treatment Effectiveness for Autism (NSTEA)
Assess the effectiveness of MTT on overall benefit (no benefit (0)/slight benefit(1)/moderate benefit (2)/good benefit (3)/great benefit (4)).
Time frame: End of Treatment (Day 104)
Social Responsiveness Scale (SRS 2)
65-item scale that assesses social impairments, a core issue in autism, including social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits.
Time frame: Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)
Aberrant Behaviour Checklist (ABC-2)
assesses problem behaviors in five areas common in individuals with ASD, including irritability, social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech.
Time frame: Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)
CAAAS (subscale on GI symptoms)
This tool assesses both core ASD symptoms and a comprehensive list of common co-occurring symptoms in ASD, including gastrointestinal, behavioral, mental health, and physical health symptoms. 9-point severity scale from "none" to "major". There is also a "change"
Time frame: Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104
Comprehensive Assessment of Autism and Associated Symptoms (CAAAS)
This tool assesses both core ASD symptoms and a comprehensive list of common co-occurring symptoms in ASD, including gastrointestinal, behavioral, mental health, and physical health symptoms. 9-point severity scale from "none" to "major". There is also a "change"
Time frame: Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104
Vineland Adaptive Behavior Scale -Third Edition (Vineland 3)
Comprehensive form consisting of 381 items covering three domains (Communication, Daily Living Skills, and Socialization) and the Maladaptive Behavior subscale (44 items).
Time frame: Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)
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