Clostridium Difficile InfectionPhase 2GRAFTNCT03621657
The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation
A Phase 2 study testing Low Dose FMT Capsule DE and Single Dose FMT Capsule DE in people with Clostridium Difficile Infection and C.Difficile Diarrhea, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The primary objective of this study is to compare the gut microbiota and clinical outcomes of oral FMT during antibiotic treatment, immediately following antibiotic treatment, and placebo. The second objective is to assess the safety and feasibility of daily oral Fecal Microbiome Transplant (FMT) as a treatment option. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection, C.Difficile Diarrhea, CDI
- What is being tested?
- Low Dose FMT Capsule DE and Single Dose FMT Capsule DE
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2019to 27 Feb 2020
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cognitively intact and willing to provide informed consent
- Willing and able to comply with all study procedures for the duration of the study
- Able to take oral medications
- Age 18 or over
- Recent CDI episode occurring in the last 180 days with completion of therapy as confirmed by the electronic medical record (EMR)
- Receiving antibiotics at enrollment for reasons other than CDI and having taken the antibiotics for no longer than 10 days.
Show all 9Show fewer
- Women of childbearing potential in a sexual relationship with men must use an acceptable method of contraception (including, but not limited to, barriers with additional spermicidal foam or jelly, intrauterine devices, hormonal contraception started at least 30 days before enrollment into the study, or intercourse with men who underwent a vasectomy) for 4 weeks following completion of the study treatment,
- Males must agree to avoid impregnation of women during and for 4 weeks following completion of the study treatment.
- Able to take the test capsule successfully with no signs or symptoms of dysphagia.
Who cannot join
- Females who are pregnant, lactating, or planning to become pregnant during the study. Female patients of childbearing potential will take a pregnancy test at the intervention visit and will be excluded if pregnant.
- Inability (e.g. dysphagia) to or unwilling to swallow capsules
- Known or suspected toxic megacolon and or known small bowel ileus
- Bowel obstruction or other gut motility issues occurring in the last two weeks taht are unresolved as noted by the patient or in the EMR
- Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment not including appendectomy or cholecystectomy.
- History of bariatric or colectomy surgery
Show all 16Show fewer
- Concurrent intensive induction chemotherapy, radiation therapy, or biologic treatment for an active malignancy. Patients on maintenance chemotherapy may be enrolled after consultation with the medical monitor.
- Expected life expectancy less than 6 months.
- Patients with severe anaphylactic or anaphylactoid food allergy.
- Solid organ transplant recipients ≤90 days post-transplant or on active treatment for rejection
- Neutropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-tumor necrosis factor (TNF) will be permitted. Patients on monoclonal antibodies to B and T cells, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhibitors (tacrolimus, cyclosporine), and mycophenolate mofetil may only be enrolled after consultation with the medical monitor.
- At risk of CMV/EBV associated disease, negative immunoglobulin gamma (IgG) testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV)
- Any other gastrointestinal illness including diarrhea
- On oral vancomycin or metronidazole
- Having been taking the currently prescribed antibiotic for over 10 days
- Any condition that would jeopardize the safety or rights of the patient, would make it unlikely for the patient to complete the study, or would confound the results of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, 53794
About this study
Official title: A Phase II Randomized, Double-blind Placebo-controlled Trial to Determine if Fecal Microbiota Transplantation is Efficacious for Hospitalized Patients With C. Difficile Infection History During Antibiotic Treatment
The primary objective of this study is to compare the gut microbiota and clinical outcomes of oral FMT during antibiotic treatment, immediately following antibiotic treatment, and placebo. The second objective is to assess the safety and feasibility of daily oral Fecal Microbiome Transplant (FMT) as a treatment option.
Read the detailed description
Clostridium difficile is the most frequent bacterial cause of antibiotic-associated diarrhea. Those with a previous C. difficile infection (CDI) are at high risk of recurrent infection. Recurrent CDI often occurs when the normal gut microbiota are disrupted. Dysbiosis of the gut microbiota predisposes to CDI which, despite treatment can recur in 30% of patients. A novel way to prevent CDI recurrence is by instilling feces from a healthy individual into the intestine of the CDI patient, thereby restoring balance in the gut microbiota. However, it is unknown whether or not fecal microbiota transplantation (FMT) is an efficacious choice for CDI recurrence prevention when used concurrently with antibiotics. We propose a pilot randomized, double-blind placebo controlled trial comparing oral FMT with placebo in patients with a history of CDI, currently undergoing antibiotic treatment. We will collect fecal samples from subjects prior to, during, and after FMT and collect metagenomics and microbiologic data on microbiota composition and function, and CDI recurrence. The trial's primary outcome is gut microbial composition and function. Secondary outcomes are feasibility and safety, and recurrent CDI during the trial period. In this 3 group study, FMT will be administered daily via oral capsules containing frozen fecal microbiota from universal donors in group 1, administered at the end of antibiotic treatment for group 2, and group 3 will receive daily placebo. The results of this study will provide the necessary pilot data to examine whether or not concurrent FMT in antibiotic treated patients who are at high risk for recurrent CDI can maintain a diverse healthy GI microbiota.
- Conditions
- Clostridium Difficile Infection, C.Difficile Diarrhea, CDI
- Being tested
- Low Dose FMT Capsule DE, Single Dose FMT Capsule DE, Placebo oral capsule
- Keywords
- FMT, Fecal Microbiota Transplant
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose FMT Capsule DEDrug
Also called FMT Capsule DE
5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course.
Single Dose FMT Capsule DEDrug
Also called FMT Capsule DE
30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment.
Placebo oral capsuleDrug
Also called Placebo
Five capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment.
| Study group | Role | What they receive |
|---|---|---|
| Low dose FMT Capsule DE | Experimental | FMT Capsule double-encapsulated (DE) by mouth, 5 capsules once daily with antibiotic, followed by 5 capsules daily for 7 days post-antibiotic Receives: Drug: Low Dose FMT Capsule DE |
| Single dose FMT Capsule DE | Active comparator | FMT Capsule DE by mouth, 30 capsules in a single one-time dose 48-72 post-antibiotic course. Receives: Drug: Single Dose FMT Capsule DE |
| Placebo Oral Capsule | Placebo comparator | Oral placebo capsules manufactured to mimic study capsule, 5 capsules daily with antibiotic course, followed by 5 capsules for 7 days post-antibiotic Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess Efficacy of Oral FMT on Composition and Function of the Gut Microbiota Compared to Placebo.
Assess microbial composition of stool using 16s targeted sequencing and shotgun metagenomics
Measured: 60 days
Secondary outcomes (3)
Comparison of Treatment-related Adverse Events in the Oral FMT Regimens Versus Placebo.
Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0, including serious adverse events, will be assessed. We will also assess proportion of newly diagnosed infectious diseases, which are considered adverse events of special interest (AESI) after randomization.
Measured: 60 days
Determine the Rate of Clostridium Difficile Infection (CDI) During Oral FMT Regimens Versus Placebo
Collection of CDI infection rates from baseline to end of study and comparison between both oral FMT groups versus placebo.
Measured: 60 days
Evaluate Time to Clostridium Difficile Infection (CDI) and/or Colonization With C. Difficile.
- difficile colonization will be detected in stool samples submitted at baseline through end of study. If patients' become colonized, time from randomization to colonization is collected. Comparisons are made between the oral FMT groups and placebo.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start21 Mar 2019
- Primary completion27 Feb 2020
- Study completion27 Feb 2020
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 Difficile InfectionStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a phase 2, double-blind, randomized, placebo-controlled trial assessing the effects of either daily (group 1) or one-time (group 2) oral FMT on the composition and function of gut microbiome compared to placebo (group 3) in a population of patients with a history of Clostridium difficile infection (CDI).
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Agency for Healthcare Research and Quality (AHRQ)
- Responsible party
- Sponsor
- Investigators
- Nasia Safdar, MD, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03621657
- Sponsor's protocol ID
- 2017-0789
- Other IDs
- A534265, SMPH/MEDICINE/INFECT DIS, 1R03HS025257-01
- Acronym
- GRAFT
- Status last verified
- Feb 2021
- First submitted
- 25 Jul 2018
- Last updated
- 15 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-blind Placebo-controlled Trial to Determine if Fecal Microbiota Transplantation is Efficacious for Hospitalized Patients With C. Difficile Infection History During Antibiotic Treatment
- ClinicalTrials.gov ID
- NCT03621657
- Acronym / sponsor ID
- GRAFT / 2017-0789
- Conditions
- Clostridium Difficile Infection, C.Difficile Diarrhea, CDI
- Keywords
- FMT, Fecal Microbiota Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Agency for Healthcare Research and Quality (AHRQ)
- Study start
- 21 Mar 2019 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 8 Aug 2018 (actual)
- Results
- Posted 15 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to compare the gut microbiota and clinical outcomes of oral FMT during antibiotic treatment, immediately following antibiotic treatment, and placebo. The second objective is to assess the safety and feasibility of daily oral Fecal Microbiome Transplant (FMT) as a treatment option.
Detailed description
Clostridium difficile is the most frequent bacterial cause of antibiotic-associated diarrhea. Those with a previous C. difficile infection (CDI) are at high risk of recurrent infection. Recurrent CDI often occurs when the normal gut microbiota are disrupted. Dysbiosis of the gut microbiota predisposes to CDI which, despite treatment can recur in 30% of patients. A novel way to prevent CDI recurrence is by instilling feces from a healthy individual into the intestine of the CDI patient, thereby restoring balance in the gut microbiota. However, it is unknown whether or not fecal microbiota transplantation (FMT) is an efficacious choice for CDI recurrence prevention when used concurrently with antibiotics. We propose a pilot randomized, double-blind placebo controlled trial comparing oral FMT with placebo in patients with a history of CDI, currently undergoing antibiotic treatment. We will collect fecal samples from subjects prior to, during, and after FMT and collect metagenomics and microbiologic data on microbiota composition and function, and CDI recurrence. The trial's primary outcome is gut microbial composition and function. Secondary outcomes are feasibility and safety, and recurrent CDI during the trial period. In this 3 group study, FMT will be administered daily via oral capsules containing frozen fecal microbiota from universal donors in group 1, administered at the end of antibiotic treatment for group 2, and group 3 will receive daily placebo. The results of this study will provide the necessary pilot data to examine whether or not concurrent FMT in antibiotic treated patients who are at high risk for recurrent CDI can maintain a diverse healthy GI microbiota.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- This is a phase 2, double-blind, randomized, placebo-controlled trial assessing the effects of either daily (group 1) or one-time (group 2) oral FMT on the composition and function of gut microbiome compared to placebo (group 3) in a population of patients with a history of Clostridium difficile infection (CDI).
| Arm | Type | Receives |
|---|---|---|
| Low dose FMT Capsule DE | Experimental | Drug: Low Dose FMT Capsule DEFMT Capsule double-encapsulated (DE) by mouth, 5 capsules once daily with antibiotic, followed by 5 capsules daily for 7 days post-antibiotic |
| Single dose FMT Capsule DE | Active comparator | Drug: Single Dose FMT Capsule DEFMT Capsule DE by mouth, 30 capsules in a single one-time dose 48-72 post-antibiotic course. |
| Placebo Oral Capsule | Placebo comparator | Drug: Placebo oral capsuleOral placebo capsules manufactured to mimic study capsule, 5 capsules daily with antibiotic course, followed by 5 capsules for 7 days post-antibiotic |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cognitively intact and willing to provide informed consent
- Willing and able to comply with all study procedures for the duration of the study
- Able to take oral medications
- Age 18 or over
- Recent CDI episode occurring in the last 180 days with completion of therapy as confirmed by the electronic medical record (EMR)
Key exclusion criteria (16 listed)
- Females who are pregnant, lactating, or planning to become pregnant during the study. Female patients of childbearing potential will take a pregnancy test at the intervention visit and will be excluded if pregnant.
- Inability (e.g. dysphagia) to or unwilling to swallow capsules
- Known or suspected toxic megacolon and or known small bowel ileus
- Bowel obstruction or other gut motility issues occurring in the last two weeks taht are unresolved as noted by the patient or in the EMR
- Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment not including appendectomy or cholecystectomy.
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 |
|---|---|---|
| Low Dose FMT Capsule DEAlso: FMT Capsule DE5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course. | Drug | Low dose FMT Capsule DE |
| Single Dose FMT Capsule DEAlso: FMT Capsule DE30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment. | Drug | Single dose FMT Capsule DE |
| Placebo oral capsuleAlso: PlaceboFive capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment. | Drug | Placebo Oral Capsule |
Primary outcome
Assess Efficacy of Oral FMT on Composition and Function of the Gut Microbiota Compared to Placebo.
Time frame: 60 days
Assess microbial composition of stool using 16s targeted sequencing and shotgun metagenomics
3 secondary outcomes
Comparison of Treatment-related Adverse Events in the Oral FMT Regimens Versus Placebo.
Time frame: 60 days
Determine the Rate of Clostridium Difficile Infection (CDI) During Oral FMT Regimens Versus Placebo
Time frame: 60 days
Evaluate Time to Clostridium Difficile Infection (CDI) and/or Colonization With C. Difficile.
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Clostridium Difficile Infection
Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
RecruitingEarly Phase 1
Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
Clostridioides Difficile Infection
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.
Nasia Safdar, MD, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose FMT Capsule DE and Single Dose FMT Capsule DE in people with Clostridium Difficile Infection and C.Difficile Diarrhea, run by University of Wisconsin, Madison 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 9 inclusion and 16 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 15 Mar 2021. 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. 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?
Yes. Results are posted in the registry (first posted 15 Mar 2021). 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?
Assess Efficacy of Oral FMT on Composition and Function of the Gut Microbiota Compared to Placebo. (time frame: 60 days). 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 15 Mar 2021.