Clostridium DifficilePhase 1/2NCT02465463
Early FMT for C.Difficile
A Phase 1/2 study testing Fecal microbiota transplant (FMT) and flexible sigmoidoscopy in people with Clostridium Difficile, run by Emory University at 1 site in United States.
Trial summary
Clostridium difficile infection (CDI) has increased worldwide in both frequency and severity. It is the leading cause of hospital acquired infection in developed countries and has been associated with at least 14,000 deaths per year in the United States. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Clostridium Difficile
- What is being tested?
- Fecal microbiota transplant (FMT) and flexible sigmoidoscopy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Nov 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following criteria to be eligible for the study:
- First or second episode of CDI responding to therapy
- Must have 2 or more of the following criteria:
- Age >65
- Severe underlying disease (measured by Horn index score of 3 or 4)
- Additional non-C.difficile antibiotic exposure during CDI episode
Show all 12Show fewer
- Use of antacids
- Previous episode of CDI
- Willingness to accept a fecal product made using unrelated donor stool and to comply with study protocol requirements
- Able to give informed consent
- Chronic infection with HIV, HBV, HCV is permitted unless the viral infection compromises the ability of the patient to safely participate in the study. Patients with a CD4 count <200 and/ or AIDS defining illness or decompensated cirrhosis will not be eligible for the study.
- Life expectancy >4 months
Who cannot join
- Any of the following: acute leukemia, history of allogenic or recent (within 6 months) autologous bone marrow transplant, or use of cytotoxic chemotherapy within 2 months
- ANC <1000/mm^3
- History of inflammatory bowel disease
- History of total colectomy
- Pregnant or nursing mothers
- History of significant food allergy to foods not excluded from the donor diet
Show all 14Show fewer
- Patient has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the results of the study
- Patients who are aged 80 years or greater
- Patients who are incarcerated
- Patient with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving consent
- Inherited/primary immune disorders
- Patients who are unwilling or unable to undergo sigmoidoscopy
- Unable to comply with protocol requirements
- Patients with untreated, in-situ colorectal cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study Examining the Safety and Efficacy of Early Fecal Transplant in Patients Infected With Clostridium Difficile at High Risk of Relapse
Clostridium difficile infection (CDI) has increased worldwide in both frequency and severity. It is the leading cause of hospital acquired infection in developed countries and has been associated with at least 14,000 deaths per year in the United States. With 3 million cases/ year, the annual cost for treating the infection is exceeding 3 billion dollars. It can also have a profound negative impact on quality of life.
The investigators believe that patients who are at high risk of relapse after a first CDI episode would benefit from early fecal microbial transplant (FMT). The proposed study will produce preliminary data regarding safety and efficacy and potential for cost effectiveness for the use of early fecal transplant in those patients with their first episode of non-refractory CDI who are predicted to have a high rate of recurrence based on previously published risk factors. The investigators will be better prepared to test the efficacy of this approach in a future multicenter clinical trial in a randomized controlled fashion.
Read more
The purpose of this study is to compare the effectiveness and safety of early fecal transplant using donor stool from a healthy person in a group of patients who are diagnosed with their first episode of Clostridium difficile infection and are predicted to have a high chance of the infection returning against a similar group of patients who receive current standard of care for treatment of C.difficile.
The investigators hypothesize:
- that clinical remission rates at 12 weeks as noted by absence of clinical symptoms and/or negative C.difficile stool polymerase chain reaction (PCR) will be greater in the experimental arm compared to the control arm
- that patients in the experimental group will have a low microbial diversity prior to FMT but will exhibit a high microbial diversity after the FMT that resembles the respective donor
- that the microbial diversity will be diminished in both groups at the time of enrollment, but the experimental group will exhibit a higher microbial diversity compared to the control population at 12 weeks
- that patients in both groups will exhibit poor quality of life at the time of enrollment, however, the experimental group will demonstrate higher quality of life compared to the control group at follow up after completion of treatment
- that costs incurred by the experimental group will be less than the control group
Read the detailed description
Treatment of CDI remains challenging, especially in those with recurrent disease. Failures rates of 20-30% with initial treatment have been reported, and up to 65% fail after a third course of antibiotics. In addition, costs of treatment, which can be upward of $3000 for a 10 day course of a single antibiotic, may leave many patients and their families financially overburdened. Use of FMT has shown to be effective with cure rates above 80%, safe even in immunocompromised patients, and cost effective in those with recurrent (3 or more) episodes of C.difficile. Emory University and Emory Clinic have performed over 100 FMT's since July 2012 for treatment of recurrent or refractory CDI and has had similar cure rates.
Current treatment approaches for CDI limit the use of fecal transplant to those who have had more than 2 recurrences with at least one failure of a 6-8 week taper with vancomycin or at least 2 episodes of severe CDI resulting in hospitalization or refractory CDI defined as moderate CDI not responding to standard therapy for at least one week (5). However, the investigators feel that by attempting to perform FMT early after a first episode in those at high risk of recurrence, decreased recurrence rates, improved quality of life, and lower health care costs will be seen.
Patients who participate will be randomized to one of two groups - one group who receives a fecal transplant and another group who will not receive a fecal transplant. A fecal transplant using a sigmoidoscopy will occur after the subjects in the fecal transplant arm complete the course of antibiotics for treatment of the C.difficile infection. Healthy stool from a donor will be infused into the colon to help replenish good bacteria that patients with C.difficile infection often do not have. The group that does not undergo FMT will take antibiotics and probiotic therapy for management of CDI as part of standard of care.
- Conditions
- Clostridium Difficile
- Being tested
- Fecal microbiota transplant (FMT), flexible sigmoidoscopy
- Keywords
- fecal microbiota transplant, probiotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal microbiota transplant (FMT)Procedure or surgery
250 mL of donor stool will be infused into the colon by flexible sigmoidoscopy
flexible sigmoidoscopyDevice
| Study group | Role | What they receive |
|---|---|---|
| FMT arm | Experimental | Patients in the experimental arm with undergo a fecal microbiota transplant (FMT) after finishing a course of antibiotics. Receives: Procedure: Fecal microbiota transplant (FMT); Device: flexible sigmoidoscopy |
| Control | No intervention | Patients in the non-interventional group will not receive a FMT but will be followed over the course of 6 months to assess for recurrence of C.difficile. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Remission Rates
Clinical remission rate is defined as the number of participants with an absence of clinical symptoms and/or negative C.difficile stool PCR.
Measured: Post-Intervention (Week 12)
Number of Participants That Experience Serious Adverse Events
A serious adverse event is any adverse experience that results in any of the following outcomes:
- Death;
- Life-threatening experience (adverse event is considered "life-threatening" if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death);
- Requires inpatient hospitalization or prolongation of existing hospitalization;
- Results in persistent or significant disability or incapacity;
- Is a congenital anomaly or birth defect;
- Is considered to be an important medical event (that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed in the definition above).
Measured: Post-Intervention (Month 6)
Change in the Shannon Diversity Index
The Shannon Diversity Index is a quantitative measure that reflects how many different types (such as species) there are in a dataset (a community). 16s ribosomal gene sequencing and metabolomic profile of the gut microbiota were analyzed for both groups using the Shannon Diversity index (H). The greater the index, the more diverse a species.
Measured: Baseline, Post-Intervention (Week 12)
Secondary outcomes (3)
Mean Short Form - 36 (SF-36) Score
SF-36: consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Post-Intervention (Week 12)
Mean Hospital Anxiety And Depression Scale (HADS) Score
The HADS is a fourteen item scale and each item on the questionnaire is scored from 0-3, from 0 = best and 3 = worst. A score can range between 0 and 21 for either anxiety or depression. Higher scores represent greater depressive/anxious symptoms.
Measured: Post-Intervention (Week 12)
Mean Cost of Treatment
Total cost was calculated as a summation of costs of medications, procedures, and fecal transplant used to treat C.difficile for each individual patient. A mean was calculated for both groups.
Measured: Post-Intervention (Month 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Clostridium DifficileStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tanvi Dhere, Emory University
- Investigators
- Tanvi Dhere, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02465463
- Sponsor's protocol ID
- IRB00077804
- Status last verified
- Jan 2018
- First submitted
- 27 Nov 2014
- Last updated
- 31 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Examining the Safety and Efficacy of Early Fecal Transplant in Patients Infected With Clostridium Difficile at High Risk of Relapse
- ClinicalTrials.gov ID
- NCT02465463
- Acronym / sponsor ID
- IRB00077804
- Conditions
- Clostridium Difficile
- Keywords
- fecal microbiota transplant, probiotic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 8 Jun 2015 (estimated)
- Results
- Posted 31 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clostridium difficile infection (CDI) has increased worldwide in both frequency and severity. It is the leading cause of hospital acquired infection in developed countries and has been associated with at least 14,000 deaths per year in the United States. With 3 million cases/ year, the annual cost for treating the infection is exceeding 3 billion dollars. It can also have a profound negative impact on quality of life.
The investigators believe that patients who are at high risk of relapse after a first CDI episode would benefit from early fecal microbial transplant (FMT). The proposed study will produce preliminary data regarding safety and efficacy and potential for cost effectiveness for the use of early fecal transplant in those patients with their first episode of non-refractory CDI who are predicted to have a high rate of recurrence based on previously published risk factors. The investigators will be better prepared to test the efficacy of this approach in a future multicenter clinical trial in a randomized controlled fashion.
The purpose of this study is to compare the effectiveness and safety of early fecal transplant using donor stool from a healthy person in a group of patients who are diagnosed with their first episode of Clostridium difficile infection and are predicted to have a high chance of the infection returning against a similar group of patients who receive current standard of care for treatment of C.difficile.
The investigators hypothesize:
- that clinical remission rates at 12 weeks as noted by absence of clinical symptoms and/or negative C.difficile stool polymerase chain reaction (PCR) will be greater in the experimental arm compared to the control arm
- that patients in the experimental group will have a low microbial diversity prior to FMT but will exhibit a high microbial diversity after the FMT that resembles the respective donor
- that the microbial diversity will be diminished in both groups at the time of enrollment, but the experimental group will exhibit a higher microbial diversity compared to the control population at 12 weeks
- that patients in both groups will exhibit poor quality of life at the time of enrollment, however, the experimental group will demonstrate higher quality of life compared to the control group at follow up after completion of treatment
- that costs incurred by the experimental group will be less than the control group
Detailed description
Treatment of CDI remains challenging, especially in those with recurrent disease. Failures rates of 20-30% with initial treatment have been reported, and up to 65% fail after a third course of antibiotics. In addition, costs of treatment, which can be upward of $3000 for a 10 day course of a single antibiotic, may leave many patients and their families financially overburdened. Use of FMT has shown to be effective with cure rates above 80%, safe even in immunocompromised patients, and cost effective in those with recurrent (3 or more) episodes of C.difficile. Emory University and Emory Clinic have performed over 100 FMT's since July 2012 for treatment of recurrent or refractory CDI and has had similar cure rates.
Current treatment approaches for CDI limit the use of fecal transplant to those who have had more than 2 recurrences with at least one failure of a 6-8 week taper with vancomycin or at least 2 episodes of severe CDI resulting in hospitalization or refractory CDI defined as moderate CDI not responding to standard therapy for at least one week (5). However, the investigators feel that by attempting to perform FMT early after a first episode in those at high risk of recurrence, decreased recurrence rates, improved quality of life, and lower health care costs will be seen.
Patients who participate will be randomized to one of two groups - one group who receives a fecal transplant and another group who will not receive a fecal transplant. A fecal transplant using a sigmoidoscopy will occur after the subjects in the fecal transplant arm complete the course of antibiotics for treatment of the C.difficile infection. Healthy stool from a donor will be infused into the colon to help replenish good bacteria that patients with C.difficile infection often do not have. The group that does not undergo FMT will take antibiotics and probiotic therapy for management of CDI as part of standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FMT arm | Experimental | Procedure: Fecal microbiota transplant (FMT), Device: flexible sigmoidoscopyPatients in the experimental arm with undergo a fecal microbiota transplant (FMT) after finishing a course of antibiotics. |
| Control | No intervention | –Patients in the non-interventional group will not receive a FMT but will be followed over the course of 6 months to assess for recurrence of C.difficile. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- First or second episode of CDI responding to therapy
- Must have 2 or more of the following criteria:
- Willingness to accept a fecal product made using unrelated donor stool and to comply with study protocol requirements
- Able to give informed consent
- Chronic infection with HIV, HBV, HCV is permitted unless the viral infection compromises the ability of the patient to safely participate in the study. Patients with a CD4 count <200 and/ or AIDS defining illness or decompensated cirrhosis will not be eligible for the study.
Key exclusion criteria (14 listed)
- Any of the following: acute leukemia, history of allogenic or recent (within 6 months) autologous bone marrow transplant, or use of cytotoxic chemotherapy within 2 months
- ANC <1000/mm^3
- History of inflammatory bowel disease
- History of total colectomy
- Pregnant or nursing mothers
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 transplant (FMT)250 mL of donor stool will be infused into the colon by flexible sigmoidoscopy | Procedure or surgery | FMT arm |
| flexible sigmoidoscopy | Device | FMT arm |
Primary outcome
Clinical Remission Rates
Time frame: Post-Intervention (Week 12)
Clinical remission rate is defined as the number of participants with an absence of clinical symptoms and/or negative C.difficile stool PCR.
Number of Participants That Experience Serious Adverse Events
Time frame: Post-Intervention (Month 6)
A serious adverse event is any adverse experience that results in any of the following outcomes: * Death; * Life-threatening experience (adverse event is considered "life-threatening" if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death); * Requires inpatient hospitalization or prolongation of existing hospitalization; * Results in persistent or significant disability or incapacity; * Is a congenital anomaly or birth defect; * Is considered to be an important medical event (that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed in the definition above).
Change in the Shannon Diversity Index
Time frame: Baseline, Post-Intervention (Week 12)
The Shannon Diversity Index is a quantitative measure that reflects how many different types (such as species) there are in a dataset (a community). 16s ribosomal gene sequencing and metabolomic profile of the gut microbiota were analyzed for both groups using the Shannon Diversity index (H). The greater the index, the more diverse a species.
3 secondary outcomes
Mean Short Form - 36 (SF-36) Score
Time frame: Post-Intervention (Week 12)
Mean Hospital Anxiety And Depression Scale (HADS) Score
Time frame: Post-Intervention (Week 12)
Mean Cost of Treatment
Time frame: Post-Intervention (Month 6)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Clostridium Difficile
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ACX-362E [Ibezapolstat] for Oral Treatment of Recurrent Clostridioides Difficile Infection
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A Study to Learn About a Clostridioides Difficile Vaccine in People 65 Years of Age and Older
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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.
Tanvi Dhere, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fecal microbiota transplant (FMT) and flexible sigmoidoscopy in people with Clostridium Difficile, run by Emory University at 1 site 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 12 inclusion and 14 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: finished, as of the sponsor's last update on 31 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 31 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Remission Rates (time frame: Post-Intervention (Week 12)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2018.