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

NCT06321796 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WCG IRB Protocol #20235847
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pitt Hopkins Syndrome

Keywords

Microbiota Transfer Therapy; Fecal Transplant; Fecal Microbiota Transplant; Intestinal Microbiota

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline (for 14 days pre-treatment) vs End of Treatment (Days 82-95 of treatment).

• Safety Measures (Adverse Events)

  Safety will be assessed based on the number of adverse events during treatment for each group (Group A and Group B). Units are number of adverse events.

  Days 0 to 99 of treatment

Secondary Outcomes (8)

• Gastrointestinal Symptom Rating Scale (GSRS)

  Baseline (pre-treatment) vs End of Treatment (After 95 days of treatment)

• Clinical Global Impression - Gastrointestinal (CGI-GI)

  Baseline (pre-treatment) vs End of Treatment (After 99 days of treatment)

• Clinical Global Impression - Pitt Hopkins (CGI-PTHS)

  Baseline (pre-treatment) vs End of Treatment (After 99 days of treatment).

• Parent Global Impressions - Pitt Hopkins: Change in Symptoms (PGI-PTHS-2-Change)

  End of Treatment (After 95 days of treatment)

• Gastrointestinal Symptoms common in Pitt Hopkins (GI-PTHS)

  Baseline (pre-treatment) vs End of Treatment (After 95 days of treatment)

Study Arms (2)

Group A: Treatment

EXPERIMENTAL

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

Combination Product: MTP-101P; Combination Product: Vancomycin; Combination Product: Magnesium Citrate; Combination Product: Antacid

Group B: Placebo

PLACEBO COMPARATOR

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

Combination Product: Magnesium Citrate; Combination Product: Antacid; 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. Duration: 12.5 Weeks

Group A: Treatment

Vancomycin COMBINATION_PRODUCT

Oral vancomycin is an antibiotic used for treating C. difficile-associated diarrhea and staphylococcal-induced enterocolitis. Duration: 10 Days

Group A: Treatment

Magnesium Citrate COMBINATION_PRODUCT

Magnesium citrate is a common over-the-counter laxative and bowel cleanse. Duration: 1 Day

Group A: Treatment; Group B: 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: 12.5 weeks

Group A: Treatment; Group B: Placebo

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: 12.5 weeks

Group B: Placebo

Placebo Vancomycin COMBINATION_PRODUCT

Same packaging and liquid carrier and flavoring used as for the oral vancomycin, but no vancomycin. Duration: 10 days

Group B: Placebo

Eligibility Criteria

• Age: 5 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children ages 5 to \<18 years and adults ages 18 to \< 55 years with Pitt Hopkins Syndrome (verified by genetic testing)
• GI disorder as defined below that has lasted for at least 2 years.
• 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.
• Review of last year of medical records by the study physician.
• 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 2 months prior to start of treatment (topical antibiotics are allowed)
• 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.
• Current severe gastrointestinal problems that require immediate hospital treatment (life-threatening)
• Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions
• Unstable, poor health (based on study physician's opinion), or active malignancy or infection.
• Recent or scheduled abdominal surgeries
• 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.
• 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, magnesium citrate, milk powder with chocolate flavoring (which are included in MTP-101P), or the antacid.
• 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.
• 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.
• Participants who are breastfeeding.

Sponsors & Collaborators

• Gut-Brain-Axis Therapeutics Inc.: lead
• Pitt Hopkins Research Foundation: collaborator

Study Sites (1)

Autism/Asperger's Research Group at Arizona State University

Tempe, Arizona, 85287, United States

RECRUITING

MeSH Terms

Conditions

Pitt-Hopkins syndrome

Interventions

Vancomycin; magnesium citrate; Antacids

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

Central Study Contacts

James B Adams

CONTACT

4809653316; jim.adams@asu.edu

Jasmine K Kirby

CONTACT

4802343767; jkkirby1@asu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: March 20, 2024
• Study Start: February 27, 2024
• Primary Completion: February 1, 2025
• Study Completion: May 1, 2025
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)