Microbiota Transfer Therapy for Pitt-Hopkins Syndrome and Gastrointestinal Disorders

Overseen By James B Adams

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Gut-Brain-Axis Therapeutics Inc.

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Ulcerative colitis, Crohn's disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not change your medications, supplements, diet, or therapies for at least 2 months before starting and during the trial, except for GI medications, which may be reduced if symptoms improve.

What data supports the effectiveness of the treatment Microbiota Transfer Therapy (MTT) for Pitt-Hopkins Syndrome and Gastrointestinal Disorders?

Research shows that Microbiota Transfer Therapy (MTT) has been effective in reducing gastrointestinal issues and symptoms in people with autism, which shares some similarities with Pitt-Hopkins Syndrome. This suggests potential benefits for gastrointestinal disorders in Pitt-Hopkins Syndrome as well. ^{1 2 3 4 5}

How is Microbiota Transfer Therapy (MTT) different from other treatments for Pitt-Hopkins Syndrome?

Microbiota Transfer Therapy (MTT) is unique because it involves transferring healthy gut bacteria from a donor to a patient to restore balance in the gut microbiome, which is not a standard treatment for Pitt-Hopkins Syndrome. This approach is novel as it targets the gut-brain connection, potentially addressing both gastrointestinal and neurological symptoms. ^{1 4 6 7 8}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for children and adults with Pitt Hopkins Syndrome, which includes intellectual disability and gastrointestinal issues like constipation. Participants should also have a history of hyperventilation or abnormal facial expressions related to the syndrome.

Inclusion Criteria

I am between 5 and 54 years old with genetically confirmed Pitt Hopkins Syndrome.

Review of last year of medical records by the study physician

I have had a gastrointestinal disorder for at least 2 years.

Exclusion Criteria

Current participation in other clinical trials

Allergy or intolerance to the study medications: vancomycin, magnesium citrate, milk powder with chocolate flavoring, or the antacid

Tube feeding if participant requires an unusual diet such as a liquid diet with low fiber

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo-Controlled Treatment

Randomized, double-blind, placebo-controlled trial with 10 days of oral vancomycin or placebo, 1 day of magnesium citrate, 4 days of high dose MTP-101P, followed by 12 weeks of lower maintenance dose of MTP-101P

14 weeks

Open-Label Observation and Cross-Over

Group A: Observation over 14 weeks. Group B: Receives the same treatment as Group A in Part 1

14 weeks

Follow-up

Participants are monitored for long-term efficacy and possible adverse effects

14 weeks

Treatment Details

Interventions

• Microbiota Transfer Therapy

Trial Overview The study tests Microbiota Transfer Therapy (MTT), involving an antibiotic called vancomycin, a bowel cleanse with magnesium citrate, followed by high then lower doses of MTP-101P with an antacid over several weeks against placebo treatments.

Participant Groups

Group I: Group A: Treatment Experimental Treatment 4 Interventions

Part 1: Blinded Treatment (14 weeks) Vancomycin, Magnesium Citrate, Antacid, MTP-101P

Group II: Group B: Placebo Placebo Group 4 Interventions

Part 1: Blinded Placebo (14 weeks) Placebo Vancomycin, Real Magnesium Citrate, Real Antacid, Placebo MTP-101P

Microbiota Transfer Therapy is already approved in United States for the following indications:

Approved in United States as Microbiota Transfer Therapy for:

• Pitt-Hopkins Syndrome with gastrointestinal disorders (constipation, bloating, abdominal pain)

Who Is Running the Clinical Trial?

Gut-Brain-Axis Therapeutics Inc.

Lead Sponsor

Trials

2

Recruited

80+

Pitt Hopkins Research Foundation

Collaborator

Trials

3

Recruited

20,000+

Pitt Hopkins Research Foundation

Collaborator

Trials

3

Recruited

20,000+

Findings from Research

Fecal microbiota transplantation (FMT) has shown clinical benefits in treating a wide range of dysbiosis-related diseases, with 782 studies reviewed covering 85 specific conditions, indicating its potential effectiveness beyond just gut health.

Innovative methodologies like washed microbiota transplantation (WMT) and colonic transendoscopic enteral tubing (TET) are enhancing the delivery and efficacy of FMT, suggesting a promising future for this therapy in various medical fields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases. Wang, Y., Zhang, S., Borody, TJ., et al.[2023]

Washed microbiota transplantation (WMT) using colonic transendoscopic enteral tubing (TET) was successfully performed in 38 children with autism spectrum disorder (ASD), achieving a 100% success rate across 124 procedures.

The TET method was found to be safe, with no severe adverse events reported, and parents expressed high satisfaction with the procedure, indicating its feasibility for treating symptoms associated with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children. Yuan, QF., Wu, HY., Chen, XY., et al.[2023]

Microbiota Transplant Therapy (MTT) has shown to be relatively safe and effective in reducing gastrointestinal disorders and autism symptoms in children, as indicated by an open-label study and a two-year follow-up.

MTT resulted in significant changes to the gut microbiome structure and increased microbial diversity, suggesting a potential mechanism for its therapeutic effects in individuals with autism spectrum disorders and chronic gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota transplant therapy and autism: lessons for the clinic. Adams, JB., Borody, TJ., Kang, DW., et al.[2020]

Fecal microbiota transplantation (FMT) is an effective method for modifying the gut microbiome and has shown promise in treating various conditions, including Clostridiodes difficile infection (CDI) and other gastrointestinal and neurological disorders.

While FMT is currently approved for CDI in Taiwan, there is a growing interest in its potential applications for other diseases, particularly in children, where data is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future applications of fecal microbiota transplantation for children. Chen, CC., Chiu, CH.[2022]

A 71-year-old male patient with Parkinson's disease and severe constipation experienced significant relief after undergoing fecal microbiota transplantation (FMT), achieving normal bowel movements within 5 minutes post-procedure.

The patient's Parkinson's symptoms, particularly tremors, improved notably within a week of FMT, suggesting that gut microbiota reconstruction may offer therapeutic benefits for Parkinson's patients with gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report. Huang, H., Xu, H., Luo, Q., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infections and shows promise for managing various extra-intestinal disorders, including metabolic diseases and neuropsychiatric conditions.

A randomized controlled trial demonstrated that FMT from lean donors improved insulin sensitivity and increased beneficial gut bacteria in individuals with metabolic syndrome, suggesting FMT's potential in treating metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation broadening its application beyond intestinal disorders. Xu, MQ., Cao, HL., Wang, WQ., et al.[2022]

Fecal microbiota transplantation (FMT) is primarily studied for conditions like Clostridium difficile infection and inflammatory bowel disease, with 84% of the 85 reports focusing on these areas, but most studies (87%) were non-randomized controlled trials.

Important methodological details about FMT, such as donor eligibility criteria and stool collection methods, are often poorly reported, which hinders the ability to replicate studies and fully understand the safety and efficacy of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review. Bafeta, A., Yavchitz, A., Riveros, C., et al.[2022]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infection (CDI), and it is now recommended for this specific use.

While FMT shows promise for other gastrointestinal conditions like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS), it is not yet recommended outside of CDI due to safety and efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update. Holleran, G., Scaldaferri, F., Ianiro, G., et al.[2018]

References

1. China pubmed.ncbi.nlm.nih.gov

Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases. [2023]

2. Egypt pubmed.ncbi.nlm.nih.gov

Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Microbiota transplant therapy and autism: lessons for the clinic. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Current and future applications of fecal microbiota transplantation for children. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation broadening its application beyond intestinal disorders. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update. [2018]