Fresh Versus Frozen Stool for Fecal Transplant in Children

Study Overview
=================
Brief Summary
-----------------
The primary goal of this study will be to assess whether stool collected and frozen from anonymous screened unrelated donors can be as effective as stool freshly collected from recipient's parents when used in Fecal Microbial Transplant for the eradication of recurrent Clostridium difficile infections in children. In the current protocols, which are more than 90% effective, each child who is receiving a fecal transplant has to provide their own donor stool, usually from a parent or close relative. This requires considerable screening costs for each case and is logistically complicated as the donor must be present and must stool just prior to the transplant. The investigators hope to show that a small number of healthy donors can provide stool samples which can be frozen and banked and then thawed for use in numerous patients. The primary goal is to show that Clostridium difficile will be eradicated as effectively (Greater than 90% success) when using the stool from the frozen donors. The study will also evaluate the inflammatory response and intestinal microbiome in young children aged 1-3 years with Clostridium difficile infections to better predict which ones will respond to fecal transplantation and which ones have incidental infections. For this question the investigators will gather stool samples to check for lactoferrin, calprotectin, and alpha1antitrypsin, and 16s ribosomal RNA analysis in children before and after the fecal transplants. The goal is to see if there is an intestinal microbiome that predisposes some children to getting sick from Clostridium difficile versus just having it incidentally.

Detailed Description
-----------------
The study is designed to enroll forty children aged 1-18 with recurrent Clostridium difficile Infection (CDI). Recurrent CDI is defined as an infection that persists after three rounds of appropriate antibiotics. Enrollees will be randomly assigned to receive Fecal Microbial Transplant using stool from either a screened relative as per current protocols versus using frozen stool that has been collected from healthy volunteers. Primary outcome will be the eradication of the Clostridium difficile as defined by elimination of diarrhea with a negative Clostridium difficile toxin stool test. Secondary outcomes will include a measure of quality of life pre and post Fecal Microbial Transplant using a validated quality of life survey instrument, the Health Act Child Health Questionnaire. The investigators will also assess for inflammation in the stool using lactoferrin and calprotectin and evaluate the stool microbiome in recipients pre and post transplant using sequencing to look for any pattern that predicts successful eradication.

Official Title
-----------------
A Comparison of Efficacy of Fresh Versus Frozen Donor Stool for Fecal Microbial Transplant in Children With Recurrent Clostridium Difficile Infections

Conditions
-----------------
Clostridium Difficile

Intervention / Treatment
-----------------
* Biological: Transplant uses frozen anonymous stool
* Biological: Transplant uses fresh familial stool


Participation Criteria
=================
Eligibility Criteria
-----------------
Eligible children between aged 1 and 18 years must have had Clostridium difficile infection that has not been eradicated despite at least two courses of antibiotics ( either metronidazole or vancomycin). Inclusion criteria: Age 1-18 years Diarrhea Positive Clostridium difficile infection using stool toxin testing Diarrhea that has improved on antibiotics but recurs when antibiotics are stopped. Willingness to undergo Fecal Microbial Transplant using frozen stool from anonymous screened donors. Exclusion Criteria: Age under 1 or over 18 No diarrhea

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transplant uses fresh familial stool<br>Undergoes Fecal Microbial Transplant using fresh stool from a screened family member Followed up and assessed for eradication of Clostridium difficile Quality of life assessed Stool assessed for inflammation and microbiome | Biological: Transplant uses fresh familial stool<br>* The intervention is using fresh familial donor stool for the fecal microbial transplant to treat recurrent CDI<br>* Other names: fecal microbila transplant;|
| Experimental: Transplant uses frozen anonymous stool<br>Undergoes Fecal Microbial Transplant using stool collected from screened anonymous donor that has been frozen until time of Fecal Microbial Transplant Followed up and assessed for eradication of Clostridium difficile Quality of life assessed Stool assessed for inflammation and microbiome | Biological: Transplant uses frozen anonymous stool<br>* The intervention is using frozen anonymous donor stool instead of fresh stool from family members for the fecal microbial transplant to treat recurrent CDI.<br>* Other names: fecal microbial transplant;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clostridium difficile (CD) Eradication; percentage of patients with negative CD toxin in stool following Fecal Microbiota Transplant | Will analyze stool sample collected 4 weeks after fecal microbiota transplant (FMT) for presence or absence of Clostridium difficile toxin. In addition, will note whether presenting symptoms improved or not after FMT. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in quality of life questionnaire scores after Fecal Microbiota Transplant | Will assess quality of life using standardized Child health Questionnaire which provides a raw score of 0-100. Investigators will compare scores of all patients before Fecal Transplant and 12 weeks after in order to mark the impact of procedure outcome on children's physical and psychological health | 12 weeks | 
| percentage of patients with stool Calprotectin levels exceeding 50 mcg/g after Fecal Microbiota Transplant | Will assess fecal Calprotectin levels in stools prior to fecal transplant and 4 weeks after | 4 weeks | 
| percentage of patients with positive Lactoferrin inflammatory marker in stools after Fecal Microbiota Transplant | Analyze stool samples for presence or absence Lactoferrin before Fecal transplant and 4 weeks after | 4 weeks |