Dosing Study of Microbiota Transplant Therapy for Children With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Autism Spectrum Disorder
- Sponsor
- Gut-Brain-Axis Therapeutics Inc.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Childhood Autism Rating Scale (CARS-2)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Child aged 4 to \< 18 years. This is 1 year younger than our previous study of MTT for children with ASD (IND 19048, protocol 2), because there were minimal adverse effects in that study, and earlier intervention may be more beneficial.
- •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 1 year.
- •No changes in medications, supplements, diet, therapies, or education in the 2 months prior to starting treatment, and no intention to change them during the clinical trial.
- •General good physical health aside from gastrointestinal problems.
- •At least two previous trials of "standard of care" GI treatments that did not alleviate GI symptoms (constipation, diarrhea, bloating, gas, reflux, and/or abdominal pain). Standard of care treatments include laxatives, stool softeners, enemas, suppositories, or similar medications.
Exclusion Criteria
- •Antibiotics in 3 months prior to treatment (does not apply to topical antibiotics).
- •Probiotics in 2 months prior to treatment, or fecal transplant in previous 12 months. Foods naturally containing probiotics such as yogurt are allowed.
- •Single-gene disorder (Fragile X, etc.).
- •Major brain malformation.
- •Tube feeding.
- •Current severe gastrointestinal problems that require immediate treatment (life-threatening).
- •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) including active malignancy or infection.
- •Recent or scheduled surgeries.
- •Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions.
Outcomes
Primary Outcomes
Childhood Autism Rating Scale (CARS-2)
Time Frame: Baseline (0-30 days prior to treatment) vs End of Treatment (Day 104)
A 15-item scale that can be used to both diagnose autism and ASD and to assess the overall severity of symptoms
Daily Stool Record (DSR)
Time Frame: Screening (0-120 days prior to Baseline) vs Baseline (0-30 days prior to treatment) vs End of Treatment (Day 104)
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.
Secondary Outcomes
- National Survey on treatment Effectiveness for Autism (NSTEA)(End of Treatment (Day 104))
- Gastrointestinal Symptom Rating Scale (GSRS)(Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104)
- CAAAS (subscale on GI symptoms)(Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104)
- Vineland Adaptive Behavior Scale -Third Edition (Vineland 3)(Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104))
- Clinical Global Impression - Gastrointestinal (CGI-GI)(Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104))
- Clinical Global Impression - Autism (CGI-A)(Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104))
- Social Responsiveness Scale (SRS 2)(Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104))
- Comprehensive Assessment of Autism and Associated Symptoms (CAAAS)(Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 104)
- Aberrant Behaviour Checklist (ABC-2)(Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104))