- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01703494
Fecal Transplant for Relapsing C. Difficile Infection
Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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The Bronx, New York, United States, 10467
- Montefiore Medical Center
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Rhode Island
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Providence, Rhode Island, United States, 02906
- The Miriam Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult outpatients (age ≥18 and <75) referred to one of the study centers after suffering a third (or further) documented episode CDI and
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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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:
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Cure
Time Frame: 8 weeks
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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.
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8 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Failure
Time Frame: 8 weeks
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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.
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8 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 6 months
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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.
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6 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lawrence J Brandt, MD, Montefiore Medical Center
- Principal Investigator: Colleen R Kelly, MD, Lifespan/ The Miriam Hospital
Publications and helpful links
General Publications
- Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 2010 May-Jun;44(5):354-60. doi: 10.1097/MCG.0b013e3181c87e02.
- Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol. 2000 Nov;95(11):3283-5. doi: 10.1111/j.1572-0241.2000.03302.x. No abstract available.
- Yoon SS, Brandt LJ. Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients. J Clin Gastroenterol. 2010 Sep;44(8):562-6. doi: 10.1097/MCG.0b013e3181dac035.
- Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012 Feb;46(2):145-9. doi: 10.1097/MCG.0b013e318234570b.
- Kelly CR, Khoruts A, Staley C, Sadowsky MJ, Abd M, Alani M, Bakow B, Curran P, McKenney J, Tisch A, Reinert SE, Machan JT, Brandt LJ. Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Ann Intern Med. 2016 Nov 1;165(9):609-616. doi: 10.7326/M16-0271. Epub 2016 Aug 23.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1R21DK093839-01A1 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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