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

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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 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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Elizabeth L Hohmann, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, Alm EJ, Gevers D, Russell GH, Hohmann EL. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis. 2014 Jun;58(11):1515-22. doi: 10.1093/cid/ciu135. Epub 2014 Apr 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: October 4, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 12, 2012

Study Record Updates

• Last Update Posted (Estimate): June 20, 2014
• Last Update Submitted That Met QC Criteria: June 18, 2014
• Last Verified: June 1, 2014

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: 2012-P-001657