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Fecal Transplant for Relapsing C. Difficile Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by The Miriam Hospital
Sponsor:
Information provided by (Responsible Party):
Colleen Kelly, The Miriam Hospital
ClinicalTrials.gov Identifier:
NCT01703494
First received: October 4, 2012
Last updated: December 28, 2012
Last verified: December 2012
  Purpose

There has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in North America over the past decade. Relapsing infection is a common problem in patients treated for CDI, often requiring prolonged and expensive courses of oral vancomycin with limited alternative treatment options. This study will determine if fecal microbiota transplantation, which involves administering fecal flora from a healthy stool donor to a patient with relapsing CDI, is an effective and safe treatment.


Condition Intervention Phase
Clostridium Difficile
Biological: Fecal Microbiota Transplantation
Biological: Sham Fecal Microbiota Transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection

Resource links provided by NLM:


Further study details as provided by The Miriam Hospital:

Primary Outcome Measures:
  • Clinical Cure [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Resolution of diarrhea (i.e., fewer than three unformed stools for two consecutive days), with maintenance of resolution for the duration of the 8 week follow-up period and no further requirements for anti-infective therapy for C. difficile infection). Subjects who meet this definition will be considered cured regardless of results of follow-up stool testing for C. difficile.


Secondary Outcome Measures:
  • Clinical Failure [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Persistence or development of diarrhea and the need for additional anti-infective therapy for C. difficile infection with or without positive stool testing (PCR) for C. difficile. Upon clinical failure, subject's treatment will be unblinded and those who received sham Fecal Microbiotia Transplantation (FMT) may chose to receive open label FMT using donor stool. Subjects, who received true FMT and develop clinical failure, may chose to undergo a second FMT using an alternate donor.


Other Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Subjects will be followed closely for significant adverse events and adverse events during the 8 week follow up period post-FMT and the development of new medical conditions/diagnoses or changes in medical conditions/medications will be determined at 6 month follow up contact. Adverse events will be tabulated by study arm.


Estimated Enrollment: 53
Study Start Date: October 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fecal Microbiota Transplantation
After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive fecal Microbiota Transplant (FMT) with a 300 mL donor fecal suspension delivered via colonoscopy.
Biological: Fecal Microbiota Transplantation
Fecal microbiota transplantation (FMT) involves administering fecal material from a healthy individual (donor) to a sick patient (with relapsing C. difficile infection) to restore missing components of normal intestinal flora. After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive fecal microbiota transplantation (FMT) with a 300 mL donor fecal suspension delivered via colonoscopy.
Other Names:
  • FMT
  • fecal bacteriotherapy
  • fecal flora reconstitution
  • stool transplant
Sham Comparator: Sham Fecal Microbiota Transplantation
After completing at least a 10 day course of vancomycin for treatment of the most recent acute severe C. difficile infection, subjects will receive a 300 mL infusion of a sham (autotransfusion) fecal solution at colonoscopy.
Biological: Sham Fecal Microbiota Transplantation
After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive a sham fecal microbiota transplantation (FMT) with a 300 mL sham fecal suspension delivered via colonoscopy. This sham solution will be a reinfusion of the subject's own stool.

Detailed Description:

Clostridium difficile is an increasingly common infection. The number of hospital discharges for which C. difficile was listed as the first diagnosis more than doubled between 2000 and 2003. In addition to occurring more frequently, there is an epidemic of serious cases which are more refractory to therapy and which have high rates of colectomy and death. Most commonly, C. difficile infection (CDI) is associated with use of antimicrobial agents that are thought to alter the normal bacterial flora of the gastrointestinal tract so as to permit colonization and/or proliferation and toxin elaboration by C. difficile. Though the precise mechanisms by which this occurs are still incompletely understood, depletion of physiologic microflora, in particular Bacteroides species may play an important role. Most patients with CDI respond to a course of oral metronidazole or vancomycin, however, up to 20% of patients relapse after initial treatment. Current guidelines recommend a tapering course of vancomycin after a second recurrence, however up to 60% of patients still do not respond to this treatment strategy or develop further recurrence after the vancomycin is stopped. Use of antimicrobials to treat CDI may predispose these patients to further relapses through the maintenance of disturbed intestinal flora and may contribute to the emerging problem of drug resistance.

"Fecal Microbiota Transplantation" (FMT) is a novel treatment approach which involves administration of feces from a healthy (donor) individual into a patient with relapsing CDI to promote recolonization with missing components of normal intestinal flora. Numerous case reports and retrospective case series have suggested benefit of FMT in patients with severe or recurrent CDI with cure rates as high as 100% and a mean cure rate of 89% for the nearly 300 cases reported in the world literature. Although efficacy has been documented in these case reports, to date there has not been a published prospective clinical trial of FMT for CDI.

The proposed study would be the first randomized, double-blind, placebo (sham) controlled clinical trial to determine whether FMT delivered at colonoscopy is effective at preventing further relapse in patients who have suffered from at least a 3rd recurrence of CDI despite receiving standard treatment. The investigators hypothesize that FMT is superior to placebo in preventing relapse after treatment of CDI with vancomycin. As a result of this study, the investigators will have preliminary efficacy data for this novel treatment approach for recurrent CDI. The investigators will be better prepared to test the efficacy of FMT in future multicenter clinical trials. This research will advance clinical care, potentially impacting the protocol for treatment of relapsing C. difficile infection worldwide. This proposal includes collaboration with an investigator capable of performing microbiome analyses on specimens collected as part of the trial and will further understanding of the intestinal microflora in health and disease.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Adult outpatients (age ≥18 and <75) referred to one of the study centers after suffering a third (or further) documented episode CDI and
  2. who have failed to maintain CDI cure after standard therapy with oral vancomycin.

    • Previous treatment with at least one course of tapered/pulse dose vancomycin as per SHEA-IDSA C difficile treatment guidelines or -Inability to taper or stop vancomycin without developing diarrhea requiring anti-infective therapy. -

Exclusion Criteria:

  • Patients who are aged 75 years or greater.
  • Patients who are pregnant
  • Patients who are nursing
  • Patients who are incarcerated
  • Patients with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving their own informed consent
  • Patients who are immunocompromised specifically:
  • HIV infection (any CD4 count)
  • AIDS-defining diagnosis or CD4<200/mm3
  • Inherited/primary immune disorders
  • Immunodeficient or Immunosuppressed due to medical condition/medication:
  • Current or recent (<3 most) treatment with anti-neoplastic agent
  • Current or recent (<3 mos) treatment with any immunosuppressant medications (including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil). Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
  • Patients with a history of severe (anaphylactic) food allergy
  • Patients who have previously undergone FMT
  • Patients who are unwilling or unable to undergo colonoscopy
  • Patients with untreated, in-situ colorectal cancer
  • Patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn‟s disease or microscopic colitis) or irritable bowel syndrome
  • Unable to comply with protocol requirements
  • Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
  • Patients with acute illness or fever on the day of planned FMT will be excluded (not undergo randomization or treatment with FMT) with the option of including that subject at a future date.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703494

Contacts
Contact: Colleen R. Kelly, MD 401-793-7080 ckelly2@lifespan.org
Contact: Joyce McKenney, MA, MPH 401-793-7884 JMcKenney@lifespan.org

Locations
United States, New York
Montefiore Medical Center Recruiting
The Bronx, New York, United States, 10467
Contact: Lawrence Brandt, MD    718-920-4846    lbrandt@montefiore.org   
Contact: Mustafa Alani       malani@montefiore.org   
Principal Investigator: Lawrence J Brandt, MD         
United States, Rhode Island
The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02906
Contact: Colleen R. Kelly, MD    401-793-7080    ckelly2@lifespan.org   
Contact: Joyce McKenney, MD    401-793-7884    JMcKenney@lifespan.org   
Principal Investigator: Colleen R. Kelly, MD         
Sponsors and Collaborators
Colleen Kelly
Investigators
Principal Investigator: Colleen R Kelly, MD Lifespan; The Miriam Hospital.
Principal Investigator: Lawrence J Brandt, MD Montefiore Medical Center
  More Information

Publications:
Responsible Party: Colleen Kelly, Clinical Assistant Professor of Medicine, The Miriam Hospital
ClinicalTrials.gov Identifier: NCT01703494     History of Changes
Other Study ID Numbers: 1R21DK093839-01A1
Study First Received: October 4, 2012
Last Updated: December 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by The Miriam Hospital:
C. difficile
fecal transplant
stool transplant
fecal flora reconstitution
fecal microbiota transplant
FMT

ClinicalTrials.gov processed this record on November 27, 2014