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

NCT ID: NCT06503978

Last Updated: 2024-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-20

Study Completion Date

2026-08-17

Brief Summary

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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

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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.

Conditions

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Autism Spectrum Disorder Gastro-Intestinal Disorder Constipation Diarrhea

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participants, Investigators and outcome assessors were all blinded. Only the Pharmacist distributing the medication knew the randomization code.

Study Groups

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Group A: Treatment (Dose 1)

Part 1: Blinded Treatment (15 weeks)

Vancomycin, Miralax, Antacid, MTP-101P

Group Type EXPERIMENTAL

MTP-101P

Intervention Type 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.

Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 14 Days

Miralax

Intervention Type COMBINATION_PRODUCT

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

Antacid

Intervention Type 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 B: Treatment (Dose 2)

Part 1: Blinded Treatment (15 weeks)

Vancomycin, Miralax, Antacid, MTP-101P

Group Type EXPERIMENTAL

MTP-101P

Intervention Type 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.

Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 14 Days

Miralax

Intervention Type COMBINATION_PRODUCT

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

Antacid

Intervention Type 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 C: Placebo

Part 1: Blinded Placebo (15 weeks)

Placebo Vancomycin, Real Miralax, Real Antacid, Placebo MTP-101P

Group Type PLACEBO_COMPARATOR

Miralax

Intervention Type COMBINATION_PRODUCT

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

Placebo MTP-101P

Intervention Type 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

Placebo Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 14 days

Group D: Placebo

Part 1: Blinded Placebo (15 weeks)

Placebo Vancomycin, Real Miralax, Real Antacid, Placebo MTP-101P

Group Type PLACEBO_COMPARATOR

Miralax

Intervention Type COMBINATION_PRODUCT

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

Placebo MTP-101P

Intervention Type 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

Placebo Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 14 days

Interventions

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MTP-101P

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.

Intervention Type COMBINATION_PRODUCT

Vancomycin

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

Duration: 14 Days

Intervention Type COMBINATION_PRODUCT

Miralax

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

Intervention Type COMBINATION_PRODUCT

Antacid

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

Intervention Type COMBINATION_PRODUCT

Placebo MTP-101P

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

Intervention Type COMBINATION_PRODUCT

Placebo Vancomycin

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

Duration: 14 days

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. 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).
3. GI disorder as defined below that has lasted for at least 1 year.
4. 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.
5. General good physical health aside from gastrointestinal problems.
6. 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

1. Antibiotics in 3 months prior to treatment (does not apply to topical antibiotics).
2. Probiotics in 2 months prior to treatment, or fecal transplant in previous 12 months. Foods naturally containing probiotics such as yogurt are allowed.
3. Single-gene disorder (Fragile X, etc.).
4. Major brain malformation.
5. Tube feeding.
6. Current severe gastrointestinal problems that require immediate treatment (life-threatening).
7. Severely underweight/malnourished (per physician clinical judgement).
8. 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.
9. Recent or scheduled surgeries.
10. Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions.
11. Current participation in other clinical trials.
12. 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).
13. 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.
14. 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.
15. Psychotropic medication daily use - Current or within 2 months prior to treatment - which are known to interfere in gastrointestinal function.
16. Evidence of significant impairment of immune system, or taking medications that can compromise the immune system, and thus increase risk if exposed to multiple-drug resistant bacteria.
17. Substantially decreased kidney function, as evidenced by estimated glomerular filtration rate of \<60 mL/min/1.73 m2. This is not normally reported for children on standard laboratory metabolic panels, so in those cases we will use the National Kidney Foundations Pediatric GFR Calculator to calculate the pediatric GFR based on age/height, the BUN and serum creatinine from our standard CMP (National Kidney Foundation Inc., n.d.). This calculator uses the Creatinine-based "Bedside Schwartz" equation (2009) that seems to be the most commonly used calculation for this purpose.
18. Participants who are breastfeeding.

The rational for exclusions 1-2 is that they interfere with gut flora. The rationale for exclusions 3-4 is that those individuals are probably less likely to respond to the proposed treatment.

The rationale for exclusions 5-9 is that those individuals are at higher risk of safety problems with MTT.

The rational for exclusion 10 is that inclusion of people with these GI conditions would complicate analysis of the study results.

The rational for exclusion 11 is that participation in other trials would interfere with the results of this one.

The rationale for exclusion 12 is to avoid risk to fetuses. The rationale for exclusion 13 is to avoid known allergic reactions to study medications.
Minimum Eligible Age

4 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gut-Brain-Axis Therapeutics Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Autism/Asperger's Research Group at Arizona State University

Tempe, Arizona, United States

Site Status

Countries

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United States

Other Identifiers

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WCG IRB #20242031

Identifier Type: -

Identifier Source: org_study_id

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