- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03621657
The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation (GRAFT)
February 19, 2021 updated by: University of Wisconsin, Madison
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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53794
- University of Wisconsin Hospital & Clinics
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Low dose FMT Capsule DE
FMT Capsule double-encapsulated (DE) by mouth, 5 capsules once daily with antibiotic, followed by 5 capsules daily for 7 days post-antibiotic
|
5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course.
Other Names:
|
ACTIVE_COMPARATOR: Single dose FMT Capsule DE
FMT Capsule DE by mouth, 30 capsules in a single one-time dose 48-72 post-antibiotic course.
|
30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment.
Other Names:
|
PLACEBO_COMPARATOR: Placebo Oral Capsule
Oral placebo capsules manufactured to mimic study capsule, 5 capsules daily with antibiotic course, followed by 5 capsules for 7 days post-antibiotic
|
Five capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
60 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of Treatment-related Adverse Events in the Oral FMT Regimens Versus Placebo.
Time Frame: 60 days
|
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.
|
60 days
|
Determine the Rate of Clostridium Difficile Infection (CDI) During Oral FMT Regimens Versus Placebo
Time Frame: 60 days
|
Collection of CDI infection rates from baseline to end of study and comparison between both oral FMT groups versus placebo.
|
60 days
|
Evaluate Time to Clostridium Difficile Infection (CDI) and/or Colonization With C. Difficile.
Time Frame: 60 days
|
C. 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.
|
60 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
March 21, 2019
Primary Completion (ACTUAL)
February 27, 2020
Study Completion (ACTUAL)
February 27, 2020
Study Registration Dates
First Submitted
July 25, 2018
First Submitted That Met QC Criteria
August 3, 2018
First Posted (ACTUAL)
August 8, 2018
Study Record Updates
Last Update Posted (ACTUAL)
March 15, 2021
Last Update Submitted That Met QC Criteria
February 19, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-0789
- A534265 (Other Identifier: UW, Madison)
- SMPH/MEDICINE/INFECT DIS (Other Identifier: UW Madison)
- 1R03HS025257-01 (AHRQ)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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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