MTT for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04132427

Enrollment

Registered

2019-10-18

Start date

2019-09-30

Completion date

2022-04-15

Last updated

2024-08-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pitt Hopkins Syndrome

Keywords

microbiota transfer therapy, fecal transplant, fecal microbiota transplant, intestinal 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

Interventions

COMBINATION_PRODUCTvancomycin, 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

COMBINATION_PRODUCTplacebo 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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Part 1 is double-blind Parts 2 and 3 are single-blind (outcomes assessor is blinded)

Intervention 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

Eligibility

Sex/Gender

ALL

Age

7 Years to 17 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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).
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.
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).
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.
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Group A: Treatment Vancomycin, magnesium citrate, microbiota 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	3
Group B: Placebo placebo vancomycin, real magnesium citrate (because it obviously empties the bowels) and placebo microbiota 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	3
Total	6

Baseline characteristics

Characteristic	Group A: Treatment	Group B: Placebo	Total
Age, Categorical <=18 years	3 Participants	3 Participants	6 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	13.0 years STANDARD_DEVIATION 3.6	12.7 years STANDARD_DEVIATION 3.1	12.8 years STANDARD_DEVIATION 3
Daily Stool Record	14 Number of abnormal days out of 14 days STANDARD_DEVIATION 0	14 Number of abnormal days out of 14 days STANDARD_DEVIATION 0	14 Number of abnormal days out of 14 days STANDARD_DEVIATION 0
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants	3 Participants	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	3 Participants	6 Participants
Region of Enrollment United States	3 participants	3 participants	6 participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants
Sex: Female, Male Male	2 Participants	2 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3
other Total, other adverse events	3 / 3	3 / 3
serious Total, serious adverse events	0 / 3	0 / 3

Outcome results

Primary

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.

Time frame: change in % abnormal days from baseline (for 2 weeks) vs. week 14 (2 weeks from week 13-14)

Arm	Measure	Value (MEAN)	Dispersion
Group A: Treatment	Daily Stool Record (DSR(	-2.3 days	Standard Deviation 2.5
Group B: Placebo	Daily Stool Record (DSR(	0 days	Standard Deviation 0

Primary

Safety Measures

number of adverse events and serious adverse events likely associated with treatment

Time frame: weeks 0-14

Arm	Measure	Value (NUMBER)
Group A: Treatment	Safety Measures	8 number of AEs among all participants
Group B: Placebo	Safety Measures	10 number of AEs among all participants

Secondary

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.