Microbiota Transfer Therapy for Children and Adults With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders

NCT ID: NCT06321796

Last Updated: 2024-03-20

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-27

Study Completion Date

2025-05-31

Brief Summary

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The investigators propose to investigate Microbiota Transfer Therapy (MTT) for treating patients with Pitt-Hopkins Syndrome (PTHS) and gastrointestinal problems (constipation, bloating, abdominal pain). MTT involves a combination of 10 days of oral vancomycin (an antibiotic to kill pathogenic bacteria), followed by 1 day of bowel cleanse using magnesium citrate, followed by 4 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 5-17 years old and adults 18-55 years old with Pitt-Hopkins Syndrome (PTHS) and Gastrointestinal (GI) problems who have attempted two standard-of-care (SOC) GI treatments with no alleviation of symptoms. This is a Phase 2 clinical trial that will evaluate the safety, tolerability, and efficacy of a powder version of Microbiota Transfer Therapy (MTT) called MTP-101P. The three parts of this trial are described below.

Part 1: Placebo-Controlled Treatment (14 Weeks) The trial will begin with a randomized, double-blind, placebo-controlled trial which will include a 10-day treatment with oral vancomycin (or placebo), then 1 day of magnesium citrate to cleanse the bowel of vancomycin and bacteria/feces (all participants, since its bowel-emptying effect cannot be blinded), followed by 4 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 vs. Group B: Placebo vancomycin, real magnesium citrate, placebo MTP-101P, real antacid.

Part 2: Open-Label Observation and Cross-Over (14 weeks) Group A: Observation over the next 14 weeks (no additional treatment). Group A completes the study at the end of part 2.

Group B: They will receive the same treatment that Group A received in part 1. This includes 10 days of vancomycin, magnesium citrate, and an initial high dose of MTP-101P for 4 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 B: There will be a follow-up evaluation 14 weeks post-treatment after the end of Part 2, to assess long-term efficacy and possible adverse effects.

Conditions

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Pitt Hopkins Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Part 1: Randomized, Double-Blinded, Placebo-Controlled Treatment (14 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

Study Groups

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Group A: Treatment

Part 1: Blinded Treatment (14 weeks)

Vancomycin, Magnesium Citrate, 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.

Duration: 12.5 Weeks

Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 10 Days

Magnesium Citrate

Intervention Type COMBINATION_PRODUCT

Magnesium citrate is a common over-the-counter laxative and bowel cleanse.

Duration: 1 Day

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: 12.5 weeks

Group B: Placebo

Part 1: Blinded Placebo (14 weeks)

Placebo Vancomycin, Real Magnesium Citrate, Real Antacid, Placebo MTP-101P

Group Type PLACEBO_COMPARATOR

Magnesium Citrate

Intervention Type COMBINATION_PRODUCT

Magnesium citrate is a common over-the-counter laxative and bowel cleanse.

Duration: 1 Day

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: 12.5 weeks

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: 12.5 weeks

Placebo Vancomycin

Intervention Type COMBINATION_PRODUCT

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

Duration: 10 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.

Duration: 12.5 Weeks

Intervention Type COMBINATION_PRODUCT

Vancomycin

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

Duration: 10 Days

Intervention Type COMBINATION_PRODUCT

Magnesium Citrate

Magnesium citrate is a common over-the-counter laxative and bowel cleanse.

Duration: 1 Day

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: 12.5 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: 12.5 weeks

Intervention Type COMBINATION_PRODUCT

Placebo Vancomycin

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

Duration: 10 days

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

1. Children ages 5 to \<18 years and adults ages 18 to \< 55 years with Pitt Hopkins Syndrome (verified by genetic testing)
2. GI disorder as defined below that has lasted for at least 2 years.
3. No changes in medications, supplements, diet, or therapies in the 2 months prior to start of treatment, and no intention to change treatments during Part 1 (all participants) and Part 2 (group B) of the clinical trial. The only exception is GI medications, which may be reduced if symptoms reduce, and any changes during the study will be documented.
4. Review of last year of medical records by the study physician.
5. 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 2 months prior to start of treatment (topical antibiotics are allowed)
2. Probiotics in 2 months prior to start of treatment, or fecal transplant in last 12 months. Foods naturally containing probiotics such as yogurt are allowed.
3. Tube feeding may be an exclusion criterion if the participant requires an unusual diet such as a liquid diet with low fiber.
4. Current severe gastrointestinal problems that require immediate hospital treatment (life-threatening)
5. Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions
6. Unstable, poor health (based on study physician's opinion), or active malignancy or infection.
7. Recent or scheduled abdominal surgeries
8. Current participation in other clinical trials
9. 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.

Males who are sexually active with a female partner without highly effective birth control (IUD or birth control hormones).
10. Allergy or intolerance to the study medications: vancomycin, magnesium citrate, milk powder with chocolate flavoring (which are included in MTP-101P), or the antacid.
11. Clinically significant abnormalities at baseline on the blood safety tests, and confirmed on a second test. The tests include Comprehensive Metabolic Panel, and Complete Blood Count with Differential. Note that some abnormalities may occur due to PTHS, so only those likely to significantly increase risk in this study would be grounds for exclusion, at the discretion of the study physician. See detailed discussion at the end of this section on Interpreting Laboratory Results. re. Eligibility for Admission to Study.
12. 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.
13. 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 Glomerular filtration rate (GFR) Calculator to calculate the pediatric GFR based on age/height, the Blood urea nitrogen (BUN) and serum creatinine from our standard Comprehensive Metabolic Panel (CMP). \[https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped\] This calculator uses the Creatinine-based "Bedside Schwartz" equation (2009) that seems to be the most commonly used calculation for this purpose.
14. Participants who are breastfeeding.
Minimum Eligible Age

5 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pitt Hopkins Research Foundation

OTHER

Sponsor Role collaborator

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 RECRUITING

Countries

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United States

Central Contacts

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James B Adams

Role: CONTACT

4809653316

Jasmine K Kirby

Role: CONTACT

4802343767

Facility Contacts

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James Adams, Phd

Role: primary

480-818-0741

Jasmine Kirby, MS

Role: backup

4802343767

Other Identifiers

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WCG IRB Protocol #20235847

Identifier Type: -

Identifier Source: org_study_id

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