The GRAFT Study: Gut RecolonizAtion by Fecal Transplantation

NCT03621657 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 2017-0789A534265SMPH/MEDICINE/INFECT DIS1R03HS025257-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Clostridium Difficile Infection; C.Difficile Diarrhea; CDI

Keywords

FMT; Fecal Microbiota Transplant

Outcome Measures

Primary Outcomes (1)

• 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

  60 days

Secondary Outcomes (3)

• Comparison of Treatment-related Adverse Events in the Oral FMT Regimens Versus Placebo.

  60 days

• Determine the Rate of Clostridium Difficile Infection (CDI) During Oral FMT Regimens Versus Placebo

  60 days

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

  60 days

Study Arms (3)

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

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.

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

Drug: Placebo oral capsule

Interventions

Low Dose FMT Capsule DE DRUG

5 FMT Capsule DE along with antibiotic; followed by five capsules FMT Capsule DE x 7 days post-antibiotic course.

Also known as: FMT Capsule DE

Low dose FMT Capsule DE

Single Dose FMT Capsule DE DRUG

30 pill FMT Capsule DE treatment x 1, 48-72 hours following completion of antibiotic treatment.

Also known as: FMT Capsule DE

Single dose FMT Capsule DE

Placebo oral capsule DRUG

Five capsules per day along with antibiotic; followed by five capsules per day for seven days post-antibiotic treatment.

Also known as: Placebo

Placebo Oral Capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (1)

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53794, United States

Location

MeSH Terms

Conditions

Clostridium Infections

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Nasia Safdar
• Organization: University of Wisconsin-Madison

ns2@medicine.wisc.edu

608-263-1545

Study Officials

• Nasia Safdar, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 8, 2018
• Study Start: March 21, 2019
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: March 15, 2021
• Results First Posted: March 15, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)