Fecal Microbiota Transplant for Relapsing Clostridium Difficile Infection in Adults and Children Using a Frozen Encapsulated 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 an inoculum administered by frozen orally-administered capsules. Subjects with recurrent/relapsing C. difficile infection will receive FMT via oral capsules 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 Clostridium Difficile Infection in Adults and Children Using a Frozen Encapsulated Inoculum

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Fecal Microbiota Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients with refractory, recurrent or relapsing C. difficile infection (CDI) defined as EITHER: At least three episodes of mild-to-moderate CDI At least two episodes of severe CDI resulting in hospitalization and associated with significant morbidity One protracted episode of CDI, defined as at least 3 weeks of ongoing Grade 3 severe symptoms of CDI despite standard antimicrobial therapy for CDI We expect that most, but not all, subjects will have tried and failed a taper of vancomycin. Willingness to accept risk of unrelated donor stool Age 7 and above. Seven is chosen as a lower limit based upon the legal age of assent. Based on the literature, most children aged 7 and above can be taught to swallow even large capsules through simple coaching techniques Able to consent for self, or parental assent/child assent as age appropriate Exclusion criteria Delayed gastric emptying syndrome Known chronic aspiration Swallowing dysfunction or oral-motor dyscoordination. Inability or unwillingness to swallow multiple large capsules Pregnant women Patients with an acute illness unrelated to CDI or an acute exacerbation of underlying comorbid condition Patients with comorbidities associated with increased risk of serious infection following bacterial translocation, including but not limited to: subjects on major immunosuppressive agents including high dose corticosteroids, calcineurin inhibitors, mTOR inhibitors, lymphocyte depleting biologic agents, anti-TNF agents, and others; chemotherapeutic anti-neoplastic agents* Patients with decompensated liver cirrhosis, advanced HIV/AIDS, recent bone marrow transplant, hypoglobulinemia or other cause of severe immunodeficiency* Patients with a history of significant allergy to foods not excluded from the donor diet

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule<br>Fecal microbiota transplant (stool transplant) from healthy, unrelated donor via frozen capsule | Drug: Fecal Microbiota Transplant<br>* Reconstitution of normal flora by a stool transplant from a healthy individual to a C. difficile - infected recipient via frozen capsule<br>* Other names: Fecal bacteriotherapy;|

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 months 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 | Up to 2 months post-FMT | 

 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