Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients

• ClinicalTrials.gov Identifier: NCT03617445
• Recruitment Status: Active, not recruiting
• First Posted: August 6, 2018
• Last Update Posted: February 8, 2023
• Sponsor: University of Wisconsin, Madison
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

Brief Summary:

The objective is to examine the effect of Fecal Microbiota Transplantation (FMT) compared with vancomycin for cure of recurrent C. diff infection (CDI) in solid organ transplant (SOT) recipients in a randomized, controlled clinical trial.

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Infection Recurrence	Drug: FMT oral capsule; Drug: Oral Vancomycin; Drug: FMT oral placebo; Drug: Oral Vancomycin placebo	Phase 2

Detailed Description:

Clostridium difficile (C.difficile) is a pathogen of major public health importance, especially in individuals with comorbid conditions such as solid organ transplantation (SOT). The incidence and adverse outcomes of CDI are greatly amplified in the setting of SOT, due to healthcare exposure, antibiotic use and immunosuppression, all of which are ubiquitous in SOT recipients. There are currently no effective treatment options to achieve a sustained cure of recurrent CDI and prevent further recurrence in SOT recipients. A novel approach that has recently gained attention is restoration of the CDI impaired gut microbiome by instillation of stool from a healthy donor into the intestine of a CDI patient. This treatment, called Fecal Microbiota Transplantation (FMT) has been found in non-comparative studies to reduce CDI recurrence dramatically with a reported efficacy of over 95%, however its efficacy in SOT recipients has not been studied and cannot be extrapolated from results in the non-SOT population because SOT recipients are a unique study population due to profound immunosuppression, frequent antibiotic use and frequent opportunities for exposure to CDI all of which markedly, repeatedly and persistently disrupt the gut microbiome. Thus, this critical gap in the field needs to be addressed by a trial of FMT in SOT recipients with CDI.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a phase 2, double blind, doubly placebo-controlled, randomized trial assessing the treatment effects of FMT compared to oral Vancomycin for recurrent CDI in solid organ transplant recipients.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients
• Actual Study Start Date: August 3, 2022
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: FMT oral capsules/ oral vancomycin placebo; FMT plus placebo vancomycin	Drug: FMT oral capsule; FMT oral capsules, single dose of 5 capsules; Other Name: MTP-101-C; Drug: Oral Vancomycin placebo; Placebo oral vancomycin capsules every 6 hours for 14 days, followed by 125 mg oral vancomycin every 12 hours for 7 days, followed by 125 mg oral vancomycin once daily for 7 days, followed by 125 mg oral vancomycin every 3 days for 14 days.; Other Name: placebo
Active Comparator: Placebo FMT capsules/ Active oral vancomycin; Vancomycin plus FMT enema placebo	Drug: Oral Vancomycin; Oral Vancomycin 125 mg capsules every 6 hours for 14 days, followed by 125 mg oral placebo every 12 hours for 7 days, followed by 125 mg oral placebo once daily for 7 days, followed by 125 mg oral placebo every 3 days for 14 days; Other Name: vancomycin; Drug: FMT oral placebo; Placebo oral capsules, single dose of 5 capsules; Other Name: Placebo MTP-101-C

Outcome Measures

Primary Outcome Measures :

1. Compare the rate of recurrence of CDI in solid organ transplant recipients with FMT compared with oral vancomycin [ Time Frame: 2 consecutive days ]
   Recurrence is defined as diarrhea (greater or equal to 3 or more loose stools that take the shape of the collection container in a 24 hr period)

Secondary Outcome Measures :

1. CDI-related QOL [ Time Frame: At baseline, week 4 and at 29 weeks ]
   Cdiff 32
2. Compare the change in gut microbiota and evaluate the association between the change in gut microbiota and recurrence of CDI [ Time Frame: up to 30 weeks of study participation ]
   Using multiple metric of microbiota structure and function
3. Evaluate the short- and medium-term safety of FMT in SOT patients [ Time Frame: Up 30 weeks of study participation ]
   Closely follow safety events
4. Compare the effects of FMT and oral vancomycin on intestinal colonization by multi-drug-resistant organisms other than C. difficile in SOT patients [ Time Frame: up to 30 weeks of study participation ]
   Analysis of stool samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Is willing to provide written informed consent.
• Is willing to comply with all study procedures and be available for the duration of the study.
• Can take oral medication
• At least 18 years of age.
• Is a solid organ transplant (SOT) recipient
• Has had at recurrent C. difficile infection defined as: positive C. difficile testing in stool and diarrhea (three or more loose stools over 24 hours) during the 180 day period following completion of treatment for prior episode
• History of positive IgG test to cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for subject or donor
• Clinical response to 4-14 days of oral antibiotic standard of care treatment for the current episode of CDI. Clinical response is defined as greater than or equal to 25% reduction of diarrhea.
• Negative urine or serum pregnancy test for women of childbearing potential and agree to use effective form of contraception until 6 weeks post treatment

Exclusion Criteria:

• Major bowel resection surgery within 90 days of randomization
• Active intestinal disease (e.g. Crohn's disease, ulcerative colitis)
• History of total colectomy or bariatric surgery
• Known or suspected toxic megacolon and/or small bowel ileus
• Presence of colostomy or ileostomy.
• Taking concomitant antibiotics within 48 hours of Visit 2. Topical antibiotics, and antibiotics for transplant prophylaxis are permitted
• Dysphagia; oropharyngeal, S), or patient has evidence of dysphagia when the 'safety test' capsule is administered
• Currently receiving medication for treatment of acute rejection and/or develop acute rejection prior to administration of FMT
• Active, Severe Gastroparesis
• Unwilling to withhold probiotics. Probiotics include supplements, prescriptions, and non-prescriptions. Foods (like yogurt) are not prohibited
• Neutropenia, ≤ 500 neutrophils/ml [noted in medical records and resulted within 7 days of Visit 1])
• Symptomatic co-infection with another intestinal pathogen as determined by chart review
• Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for any active malignancy. Patients on maintenance chemotherapy could be enrolled after consultation with the study Medical Monitor
• Any severe food allergy, defined as a history of anaphylaxis, systemic urticarial or angioedema attributed to a food and requiring current avoidance precautions
• Expected life expectancy is less than 6 months
• Use of investigational drugs, biologics, or devices within 30 days prior to randomization.
• Women who are pregnant, lactating or planning on becoming pregnant during the study
• Not suitable for study participation due to other reasons at the discretion of the investigators

Contacts and Locations

Locations

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55902

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

United States, Wisconsin

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

University of Wisconsin, Madison

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Nasia Safdar, MD, PhD; University of Wisconsin, Madison

  Study Documents (Full-Text)

Documents provided by University of Wisconsin, Madison:

Study Protocol  [PDF] August 24, 2022

More Information

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT03617445
• Other Study ID Numbers: 2018-1056; A534265 ( Other Identifier: UW Madison ); SMPH/MEDICINE/INFECT DIS ( Other Identifier: UW Madison ); Protocol Version 8/24/2022 ( Other Identifier: UW Madison ); 1U01AI125053-01A1 ( U.S. NIH Grant/Contract )
• First Posted: August 6, 2018
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; Clostridium Infections; Recurrence; Disease Attributes; Pathologic Processes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents