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The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation (GRAFT)

Primary Purpose

Clostridium Difficile Infection, C.Difficile Diarrhea, CDI

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Low Dose FMT Capsule DE
Single Dose FMT Capsule DE
Placebo oral capsule
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile Infection focused on measuring FMT, Fecal Microbiota Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Wisconsin Hospital & Clinics

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Low dose FMT Capsule DE

Single dose FMT Capsule DE

Placebo Oral Capsule

Arm Description

FMT Capsule double-encapsulated (DE) by mouth, 5 capsules once daily with antibiotic, followed by 5 capsules daily for 7 days post-antibiotic

FMT Capsule DE by mouth, 30 capsules in a single one-time dose 48-72 post-antibiotic course.

Oral placebo capsules manufactured to mimic study capsule, 5 capsules daily with antibiotic course, followed by 5 capsules for 7 days post-antibiotic

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
Evaluate Time to Clostridium Difficile Infection (CDI) and/or Colonization With C. Difficile.
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.

Full Information

First Posted
July 25, 2018
Last Updated
February 19, 2021
Sponsor
University of Wisconsin, Madison
Collaborators
Agency for Healthcare Research and Quality (AHRQ)
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1. Study Identification

Unique Protocol Identification Number
NCT03621657
Brief Title
The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation
Acronym
GRAFT
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
March 21, 2019 (Actual)
Primary Completion Date
February 27, 2020 (Actual)
Study Completion Date
February 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Agency for Healthcare Research and Quality (AHRQ)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection, C.Difficile Diarrhea, CDI
Keywords
FMT, Fecal Microbiota Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low dose FMT Capsule DE
Arm Type
Experimental
Arm Description
FMT Capsule double-encapsulated (DE) by mouth, 5 capsules once daily with antibiotic, followed by 5 capsules daily for 7 days post-antibiotic
Arm Title
Single dose FMT Capsule DE
Arm Type
Active Comparator
Arm Description
FMT Capsule DE by mouth, 30 capsules in a single one-time dose 48-72 post-antibiotic course.
Arm Title
Placebo Oral Capsule
Arm Type
Placebo Comparator
Arm Description
Oral placebo capsules manufactured to mimic study capsule, 5 capsules daily with antibiotic course, followed by 5 capsules for 7 days post-antibiotic
Intervention Type
Drug
Intervention Name(s)
Low Dose FMT Capsule DE
Other Intervention Name(s)
FMT Capsule DE
Intervention Description
5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course.
Intervention Type
Drug
Intervention Name(s)
Single Dose FMT Capsule DE
Other Intervention Name(s)
FMT Capsule DE
Intervention Description
30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Other Intervention Name(s)
Placebo
Intervention Description
Five capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment.
Primary Outcome Measure Information:
Title
Assess Efficacy of Oral FMT on Composition and Function of the Gut Microbiota Compared to Placebo.
Description
Assess microbial composition of stool using 16s targeted sequencing and shotgun metagenomics
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Comparison of Treatment-related Adverse Events in the Oral FMT Regimens Versus Placebo.
Description
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.
Time Frame
60 days
Title
Determine the Rate of Clostridium Difficile Infection (CDI) During Oral FMT Regimens Versus Placebo
Description
Collection of CDI infection rates from baseline to end of study and comparison between both oral FMT groups versus placebo.
Time Frame
60 days
Title
Evaluate Time to Clostridium Difficile Infection (CDI) and/or Colonization With C. Difficile.
Description
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.
Time Frame
60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nasia Safdar, MD, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin Hospital & Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53794
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation

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