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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Cognitively intact and willing to provide informed consent
  2. Willing and able to comply with all study procedures for the duration of the study
  3. Able to take oral medications
  4. Age 18 or over
  5. Recent CDI episode occurring in the last 180 days with completion of therapy as confirmed by the electronic medical record (EMR)
  6. Receiving antibiotics at enrollment for reasons other than CDI and having taken the antibiotics for no longer than 10 days.
  7. 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,
  8. Males must agree to avoid impregnation of women during and for 4 weeks following completion of the study treatment.
  9. Able to take the test capsule successfully with no signs or symptoms of dysphagia.

Exclusion Criteria:

  1. 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.
  2. Inability (e.g. dysphagia) to or unwilling to swallow capsules
  3. Known or suspected toxic megacolon and or known small bowel ileus
  4. 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
  5. Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment not including appendectomy or cholecystectomy.
  6. History of bariatric or colectomy surgery
  7. 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.
  8. Expected life expectancy less than 6 months.
  9. Patients with severe anaphylactic or anaphylactoid food allergy.
  10. Solid organ transplant recipients ≤90 days post-transplant or on active treatment for rejection
  11. 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.
  12. At risk of CMV/EBV associated disease, negative immunoglobulin gamma (IgG) testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV)
  13. Any other gastrointestinal illness including diarrhea
  14. On oral vancomycin or metronidazole
  15. Having been taking the currently prescribed antibiotic for over 10 days
  16. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Low Dose FMT Capsule DE
5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course.
Other Names:
  • FMT Capsule DE
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.
Drug: Single Dose FMT Capsule DE
30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment.
Other Names:
  • FMT Capsule DE
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
Drug: Placebo oral capsule
Five capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Wisconsin, Madison

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Agency for Healthcare Research and Quality (AHRQ)

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 21, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 27, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 27, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 25, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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