Clostridium DifficilePhase 2NCT01703494
Fecal Transplant for Relapsing C. Difficile Infection
A Phase 2 study testing Fecal Microbiota Transplantation in people with Clostridium Difficile, run by Colleen Kelly at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Clostridium Difficile
- What is being tested?
- Fecal Microbiota Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2012to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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. -
Who cannot join
- 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:
Show all 20Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Miriam Hospital
Providence, Rhode Island, 02906
Montefiore Medical Center
The Bronx, New York, 10467
About this study
Official title: Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection
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.
Read the 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.
- Conditions
- Clostridium Difficile
- Being tested
- Fecal Microbiota Transplantation, Sham Fecal Microbiota Transplantation
- Keywords
- C. difficile, fecal transplant, stool transplant, fecal flora reconstitution, fecal microbiota transplant, FMT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbiota TransplantationBiological
Also called FMT, fecal bacteriotherapy, fecal flora reconstitution, stool transplant
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.
Sham Fecal Microbiota TransplantationBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Fecal Microbiota Transplantation | Active comparator | 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. Receives: Biological: Fecal Microbiota Transplantation |
| Sham Fecal Microbiota Transplantation | Sham comparator | 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. Receives: Biological: Sham Fecal Microbiota Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Cure
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.
Measured: 8 weeks
Secondary outcomes (1)
Clinical Failure
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionMay 2015
- Study completionSep 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Clostridium DifficileStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Colleen Kelly
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Colleen Kelly, The Miriam Hospital
- Investigators
- Colleen R Kelly, MD, Principal investigator, Lifespan/ The Miriam HospitalLawrence J Brandt, MD, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01703494
- Sponsor's protocol ID
- 1R21DK093839-01A1
- Status last verified
- Sep 2015
- First submitted
- 4 Oct 2012
- Last updated
- 1 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 20048681Persky 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.
PubMed 11095355Yoon 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.
PubMed 20463588Kelly 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.
PubMed 22157239Kelly 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.
PubMed 27547925
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection
- ClinicalTrials.gov ID
- NCT01703494
- Acronym / sponsor ID
- 1R21DK093839-01A1
- Conditions
- Clostridium Difficile
- Keywords
- C. difficile, fecal transplant, stool transplant, fecal flora reconstitution, fecal microbiota transplant, FMT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Colleen KellyUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Sep 2015 (estimated)
- First posted
- 10 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal Microbiota Transplantation | Active comparator | Biological: Fecal Microbiota TransplantationAfter 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. |
| Sham Fecal Microbiota Transplantation | Sham comparator | Biological: Sham Fecal Microbiota TransplantationAfter 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Microbiota TransplantationAlso: FMT, fecal bacteriotherapy, fecal flora reconstitution, stool transplantFecal 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. | Biological | Fecal Microbiota Transplantation |
| Sham Fecal Microbiota TransplantationAfter 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. | Biological | Sham Fecal Microbiota Transplantation |
Primary outcome
Clinical Cure
Time frame: 8 weeks
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.
1 secondary outcome
Clinical Failure
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2015.
- Background: PubMed 20048681Khoruts 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.
- Background: PubMed 11095355Persky 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.
- Background: PubMed 20463588Yoon 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.
- Background: PubMed 22157239Kelly 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.
- Derived from this study: PubMed 27547925Kelly 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colleen R Kelly, MD principal investigator
Lifespan/ The Miriam Hospital
Lawrence J Brandt, MD principal investigator
Montefiore Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fecal Microbiota Transplantation in people with Clostridium Difficile, run by Colleen Kelly at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Cure (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01703494, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2015.