Fecal Microbiota Transplant (FMT) for Relapsing C. Difficile Infection in Adults and Children Using a Frozen Inoculum

Study Overview
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Brief Summary
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Fecal microbiota transplantation (FMT) is the reconstitution of normal flora by a stool transplant from a healthy individual to a C. difficile-infected recipient, and has long been a successful approach to recurrent/refractory C. difficile. The purpose of this project is to generate a frozen FMT inoculum from well-screened healthy volunteer donors which can be used repeatedly, particularly in those who do not have a healthy intimate partner or other related donor. Delivery of FMT has been performed colonoscopically, by fecal retention enema, or by the nasogastric route. This study will evaluate the safety and secondarily the efficacy of a frozen inoculum administered by nasogastric tube vs administered by colonoscope. Subjects with recurrent/relapsing C. difficile infection (10 per group) will receive FMT via either: colonoscopy NGT The primary endpoint is assessment of safety as measured by clinical events (GI, procedural, systemic). Efficacy will be defined as a resolution of diarrhea off antibiotics for C. difficile, in the absence of a need for OTHER systemic antibiotics, i.e. resumption of a normal bowel status for the individual. Secondary efficacy endpoints include weight, subjective well-being and relative clinical improvement per standardized questionnaire, and subject qualitative assessment of, and satisfaction with, the transplant procedures. Subjects will be monitored for clinical safety by history and standard exams and the follow-up questionnaire as well as followed closely by phone and in person.

Official Title
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Fecal Microbiota Transplant (FMT) for Relapsing C. Difficile Infection in Adults and Children Using a Frozen Inoculum

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Fecal Microbiota Transplant (FMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with recurrent or relapsing CDI defined as EITHER(13): At least three episodes of mild-to-moderate CDI and failure of a 6-8 week taper with vancomycin with or without an alternative antibiotic (e.g. rifaximin, nitazoxanide). At least two episodes of severe CDI resulting in hospitalization and associated with significant morbidity. Willingness to accept risk of unrelated donor stool Willingness to be randomized to NGT vs. colonoscopic delivery. Able to consent for self, or parental assent/child assent as age appropriate. Exclusion Criteria: Anatomic contraindication to NGT Delayed gastric emptying syndrome Known chronic aspiration Contraindication to colonoscopy (ASA 4 or more) High risk of bacterial translocation (Immunosuppression, cirrhosis etc) Pregnant or breastfeeding women Acute unrelated infection or comorbid illness exaccerbation

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colonoscopy<br>Fecal microbiota transplant (stool transplant) from healthy, unrelated donor via colonoscopy | Drug: Fecal Microbiota Transplant (FMT)<br>* Reconstitution of normal flora by a stool transplant from a healthy individual to a C. difficile - infected recipient via colonoscopy or nasogastric tube<br>|
| Experimental: Nasogastric Tube (NGT)<br>Fecal microbiota transplant (stool transplant) from healthy, unrelated donor via NGT | Drug: Fecal Microbiota Transplant (FMT)<br>* Reconstitution of normal flora by a stool transplant from a healthy individual to a C. difficile - infected recipient via colonoscopy or nasogastric tube<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety is assessed by clinical symptoms, exam, signs (GI and systemic) | up to 6 mo post FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Efficacy is defined as resolution of C. Difficile signs and symptoms off antibiotics for C. difficile | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Microbiota Transplant, Clostridium difficile, Diarrhea