MTT for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders

Phase 2

Completed

Interventions: Combination Product: placebo vancomycin, real magnesium citrate, placebo microbiota
Combination Product: vancomycin, magnesium citrate, microbiota

Brief Summary: 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: For children ages 5-17 years with PTHS and gastrointestinal problems, a Phase 2 clinical trial will evaluate the safety, tolerability, and efficacy of MTT.

Randomized, double-blind, placebo-Controlled Treatment (14 weeks)

The trial will be 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

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Group B: Placebo	placebo vancomycin, real magnesium citrate, placebo microbiota	placebo vancomycin, real magnesium citrate (because it obviously empties the bowels) and placebo microbiota
Group A: Treatment	vancomycin, magnesium citrate, microbiota	Vancomycin, magnesium citrate, microbiota

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
CGI for GI Disorders	change in score between baseline and week 14	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.
CGI for PTHS Symptoms	change in score between baseline and week 14	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.
GSRS	change in score between baseline and week 14	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). The average score for all 15 items is reported here.
PGI-PTHS	change in score between baseline and week 14	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).
FLACC	change in score between baseline and week 14	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 (zero to 10).