MTT for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders

Study Overview
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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 similar to Irritable Bowel Syndrome (IBS). MTT involves a combination of 10 days of oral vancomycin (an antibiotic to kill pathogenic bacteria), followed by a bowel cleanse, followed by 12 weeks of Fecal Microbiota (FM).

Detailed Description
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For children ages 5-17 years with PTHS and gastrointestinal problems, a a Phase 2 clinical trial will evaluate the safety, tolerability, and efficacy of MTT. 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 oral administration of FM (or placebo). An initial high dose of FM (or placebo) for two days will be followed by a lower maintenance dose of FM (or placebo) for 12 weeks. Group A: real treatment Group B: placebo vancomycin, real magnesium citrate, placebo FM Part 2 Open-Label Observation and Cross-Over (14 weeks) Group 1: Observation over the next 14 weeks (no additional treatment) Group 2: They will receive the same treatment that group A received in part 1. This includes 10 days of vancomycin, magnesium citrate, an initial high dose of FM for 4 days, and then a lower dose of FM for 12 weeks. Part 3: Follow-up There will be a follow-up evaluation at 14 weeks after the end of part 2, to assess long-term efficacy and possible adverse effects.

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

Conditions
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Pitt Hopkins Syndrome

Intervention / Treatment
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* Combination Product: vancomycin, magnesium citrate, microbiota
* Combination Product: placebo vancomycin, real magnsium citrate, placebo microbiota


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 7-17 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 last 2 months, and no intention to change them during the Parts 1 and 2 of the clinical trial. Ability to swallow pills (without chewing) Review of last two years of medical records by the study physician. Exclusion Criteria: Antibiotics in last 3 months Probiotics in last 2 months, or fecal transplant in last 12 months Tube feeding Severe gastrointestinal problems that require immediate 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) Recent or scheduled surgeries Current participation in other clinical trials Females who are pregnant or who are at risk of pregnancy and sexually active without effective birth control. Allergy or intolerance to vancomycin or magnesium citrate Clinically significant abnormalities at baseline on two blood safety tests: Comprehensive Metabolic Panel, and Complete Blood Count with Differential. 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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1: Randomized, double-blind, placebo-controlled Part 2: Treatment group enters observation, placebo group switched to treatment Part 3: Long-term observation
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Treatment<br>Vancomycin, magnesium citrate, microbiota | Combination Product: vancomycin, magnesium citrate, microbiota<br>* 10 days of oral vancomycin, then 1 day of oral magnesium citrate, , then 4 days of high-dose oral microbiota, followed by 12 weeks of low-dose oral microbiota<br>|
| Placebo Comparator: Group B: Placebo<br>placebo vancomycin, real magnesium citrate (because it obviously empties the bowels) and placebo microbiota | Combination Product: placebo vancomycin, real magnsium citrate, placebo microbiota<br>* 10 days of oral placebo vancomycin, then 1 day of oral real magnesium citrate, , then 4 days of high-dose oral placebo microbiota, followed by 12 weeks of low-dose oral placebo microbiota<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Stool Record (DSR( | The DSR is a daily record of their bowel movements including Bristol Stool Form scale. It is rated as the % of days with an abnormal report (abnormal stool, no stool, or the use of a gastrointestinal treatment). A higher percentage indicates worse symptoms.. | change in % abnormal days from baseline (for 2 weeks) vs. week 14 (2 weeks from week 13-14) | 
| Safety Measures | number of adverse events and serious adverse events likely associated with treatment | weeks 0-14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI for GI Disorders | Clinical Global Impressions of GI Disorders, including severity, change in severity, and side effects. The severity is rated on a scale of 1-7, with 1 being normal and 7 being the worst possible. | change in score between baseline and week 14 | 
| CGI for PTHS Symptoms | Clinical Global Impressions of Pitt Hopkins Syndrome symptoms, including severity, change in severity, and side effects. The severity is rated on a scale of 1-7, with 1 being normal and 7 being the worst possible. | change in score between baseline and week 14 | 
| PGI-PTHS | Parent Global Impressions of Pitt Hopkins Syndrome symptoms. This is a rating of 29 symptoms, and an average is computed. The scale ranges from -3 (much worse) to +3 (much better). | change in score between baseline and week 14 | 
| GSRS | Gastrointestinal Symptom Rating Scale. This is a 15-item questionnaire, with each item rated on a scale of 1 (no symptoms) to 7 (very severe discomfort). | change in score between baseline and week 14 | 
| FLACC | Revised Face Legs Activity Crying Consolability Pain Questionnaire for Children with Cognitive Impairment (FLACC). This is a rating scale of 5 symptoms of pain, with each item rated on a scale of 0 (no symptom) to 2 (maximum symptom), and the scores for each item are summed to create a total score. | change in score between baseline and week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota transfer therapy, fecal transplant, fecal microbiota transplant, intestinal microbiota