Fecal Microbiota Transplant for Relapsing Clostridium Difficile Infection in Adults and Children Using a Frozen Encapsulated Inoculum

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

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: Fecal Microbiota Transplant

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. Erratum In: JAMA. 2015 Feb 17;313(7):729.

Helpful Links

• JAMA paper

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 31, 2013
• First Submitted That Met QC Criteria: August 1, 2013
• First Posted (Estimate): August 2, 2013

Study Record Updates

• Last Update Posted (Estimate): July 19, 2016
• Last Update Submitted That Met QC Criteria: July 15, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Diarrhea; Clostridium difficile; Fecal Microbiota Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections
• Other Study ID Numbers: 2013-P-001355