Microbiota Transplant Therapy for Children With Both Autism Spectrum Disorder and Gastrointestinal Disorders

NCT06503978 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WCG IRB #20242031
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder; Gastro-Intestinal Disorder; Constipation; Diarrhea

Keywords

fecal transplant; fecal microbiota transplant

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Screening (0-120 days prior to Baseline) vs Baseline (0-30 days prior to treatment) vs End of Treatment (Day 104)

Secondary Outcomes (9)

• Gastrointestinal Symptom Rating Scale (GSRS)

  Baseline (0-30 days prior to treatment) VS Day 14, 28,56,84 and 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)

• National Survey on treatment Effectiveness for Autism (NSTEA)

  End of Treatment (Day 104)

• Social Responsiveness Scale (SRS 2)

  Baseline (0-30 days prior to treatment) VS End of Treatment (Day 104)

Study Arms (4)

Group A: Treatment (Dose 1)

EXPERIMENTAL

Part 1: Blinded Treatment (15 weeks) Vancomycin, Miralax, Antacid, MTP-101P

Combination Product: MTP-101P; Combination Product: Vancomycin; Combination Product: Miralax; Combination Product: Antacid

Group B: Treatment (Dose 2)

EXPERIMENTAL

Part 1: Blinded Treatment (15 weeks) Vancomycin, Miralax, Antacid, MTP-101P

Combination Product: MTP-101P; Combination Product: Vancomycin; Combination Product: Miralax; Combination Product: Antacid

Group C: Placebo

PLACEBO COMPARATOR

Part 1: Blinded Placebo (15 weeks) Placebo Vancomycin, Real Miralax, Real Antacid, Placebo MTP-101P

Combination Product: Miralax; Combination Product: Placebo MTP-101P; Combination Product: Placebo Vancomycin

Group D: Placebo

PLACEBO COMPARATOR

Part 1: Blinded Placebo (15 weeks) Placebo Vancomycin, Real Miralax, Real Antacid, Placebo MTP-101P

Combination Product: Miralax; Combination Product: Placebo MTP-101P; Combination Product: Placebo Vancomycin

Interventions

MTP-101P COMBINATION_PRODUCT

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.

Group A: Treatment (Dose 1); Group B: Treatment (Dose 2)

Vancomycin COMBINATION_PRODUCT

Oral vancomycin is an antibiotic used for treating C. difficile-associated diarrhea and staphylococcal-induced enterocolitis. Duration: 14 Days

Group A: Treatment (Dose 1); Group B: Treatment (Dose 2)

Miralax COMBINATION_PRODUCT

Miralax is a common over-the-counter laxative and bowel cleanse

Group A: Treatment (Dose 1); Group B: Treatment (Dose 2); Group C: Placebo; Group D: Placebo

Antacid COMBINATION_PRODUCT

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

Group A: Treatment (Dose 1); Group B: Treatment (Dose 2)

Placebo MTP-101P COMBINATION_PRODUCT

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

Group C: Placebo; Group D: Placebo

Placebo Vancomycin COMBINATION_PRODUCT

Same packaging and liquid carrier and flavoring used as for the oral vancomycin, but no vancomycin. Duration: 14 days

Group C: Placebo; Group D: Placebo

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Current participation in other clinical trials.
• Females who are pregnant or who are at risk of pregnancy and sexually active with a male partner without effective birth control. We will conduct a pregnancy test on all female participants 12 years and older as part of the screening and at each clinical visit.
• a. Males who are sexually active with a female partner without highly effective birth control (IUD or birth control hormones).
• Allergy or intolerance to the study medications: vancomycin, Miralax, milk powder with soy and chocolate flavoring (which are included in MTP-101P), or the antacid. People with a known allergy or intolerance to milk, soy, or chocolate will be excluded from the study and will not participate in the tolerance test.
• Clinically significant abnormalities at baseline on blood safety tests: Comprehensive Metabolic Panel and Complete Blood Count with Differential. If there is a clinically significant result, a second test may be used to confirm that result at the physician's discretion.

Sponsors & Collaborators

• Gut-Brain-Axis Therapeutics Inc.: lead

Study Sites (1)

Autism/Asperger's Research Group at Arizona State University

Tempe, Arizona, 85287, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Digestive System Diseases; Constipation; Diarrhea

Interventions

Vancomycin; polyethylene glycol 3350; Antacids

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Gastrointestinal Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, Investigators and outcome assessors were all blinded. Only the Pharmacist distributing the medication knew the randomization code.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1: Randomized, Double-Blinded, Placebo-Controlled with 2 Treatment groups and 2 Placebo Groups (15 weeks) Part 2: Open-Label Observation and Cross-over or Treatment Part 3: Follow Up (Group B Only)

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 16, 2024
• Study Start: August 20, 2024
• Primary Completion: July 17, 2025
• Study Completion (Estimated): August 17, 2026
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)