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

Clostridium Difficile Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01914731
• Other study ID #: 2013-P-001355
• Status: Completed
• Phase: Phase 1
• First received: July 31, 2013
• Last updated: July 15, 2016
• Start date: August 2013
• Est. completion date: October 2014

Study information

• Verified date: July 2016
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 90 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Communicable Diseases
• Infection

Intervention

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

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Safety is assessed by clinical symptoms, exam, signs (GI and systemic)	Up to 6 months post-FMT	Yes
Secondary	Efficacy	Efficacy is defined as resolution of C. Difficile signs and symptoms off antibiotics for C. difficile	Up to 2 months post-FMT	No

External Links

•   JAMA paper