MTT for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders

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

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).

Study Overview

• Status: Completed
• Conditions: Pitt Hopkins Syndrome
• Intervention / Treatment: Combination product: vancomycin, magnesium citrate, microbiota; Combination product: placebo vancomycin, real magnesium citrate, placebo microbiota

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

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Children ages 7-17 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 last 2 months, and no intention to change them during the Parts 1 and 2 of the clinical trial.
4. Ability to swallow pills (without chewing)
5. Review of last two years of medical records by the study physician.

Exclusion Criteria:

1. Antibiotics in last 3 months
2. Probiotics in last 2 months, or fecal transplant in last 12 months
3. Tube feeding
4. Severe gastrointestinal problems that require immediate 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)
7. Recent or scheduled surgeries
8. Current participation in other clinical trials
9. Females who are pregnant or who are at risk of pregnancy and sexually active without effective birth control.
10. Allergy or intolerance to vancomycin or magnesium citrate
11. Clinically significant abnormalities at baseline on two blood safety tests: Comprehensive Metabolic Panel, and Complete Blood Count with Differential.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Treatment; Vancomycin, magnesium citrate, microbiota	Combination product: vancomycin, magnesium citrate, microbiota; 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
Placebo Comparator: Group B: Placebo; placebo vancomycin, real magnesium citrate (because it obviously empties the bowels) and placebo microbiota	Combination product: placebo vancomycin, real magnesium citrate, placebo microbiota; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measures	number of adverse events and serious adverse events likely associated with treatment	weeks 0-14
Daily Stool Record (DSR(	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.	change in % abnormal days from baseline (for 2 weeks) vs. week 14 (2 weeks from week 13-14)

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). The average score for all 15 items is reported here.	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 (zero to 10).	change in score between baseline and week 14

Collaborators and Investigators

• Sponsor: Arizona State University
• Collaborators: Pitt Hopkins Research Foundation

Publications and helpful links

Helpful Links

• link for our research group

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): March 17, 2022
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: fecal transplant; intestinal microbiota; microbiota transfer therapy; fecal microbiota transplant
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease Attributes; Disease; Signs and Symptoms, Respiratory; Neurodevelopmental Disorders; Syndrome; Gastrointestinal Diseases; Digestive System Diseases; Intellectual Disability; Facies; Hyperventilation; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Anticoagulants; Chelating Agents; Sequestering Agents; Cathartics; Calcium Chelating Agents; Vancomycin; Citric Acid; Sodium Citrate; Magnesium citrate
• Other Study ID Numbers: IRB#: 120190263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No