Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients
- Conditions
- Clostridium Difficile Infection Recurrence
- Interventions
- Registration Number
- NCT03617445
- Lead Sponsor
- University of Wisconsin, Madison
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FMT oral capsules/ oral vancomycin placebo FMT oral capsule FMT plus placebo vancomycin Placebo FMT capsules/ Active oral vancomycin FMT oral placebo Vancomycin plus FMT enema placebo Placebo FMT capsules/ Active oral vancomycin Oral Vancomycin Vancomycin plus FMT enema placebo FMT oral capsules/ oral vancomycin placebo Oral Vancomycin placebo FMT plus placebo vancomycin
- Primary Outcome Measures
Name Time Method Compare the Rate of Recurrence of CDI in Solid Organ Transplant Recipients With FMT Compared With Oral Vancomycin 60 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
Name Time Method CDI-related Quality of Life (QOL) Compared Using Treatment and Time Interaction as Model Terms While Adjusting for Potential Confounders Weeks 4, 29 weeks Cdiff32 32-item questionnaire, with a range of 0 to 100, with 100 representing the best score, and 0 representing the worst score. Dietary component of the questionnaire linked to any stool microbiome data to determine whether diet influences gut microbiota.
Compare the Change in Gut Microbiota and Evaluate Changes in Microbiota to Assess for Safety of FMT in Patients up to 30 weeks of study participation Using multiple metric of microbiota structure and function, analyze gut microbiome samples to evaluate the association between change in gut microbiome and recurrent CDI
Number of Patients Who Experienced Short or Medium Term Adverse Events Up 30 weeks of study participation List and evaluate all short- and medium-term safety events as defined in the study protocol for the safety of FMT in SOT patients
Compare the Effects of FMT and Oral Vancomycin on Intestinal Colonization by Multi-drug-resistant Organisms Other Than C. Difficile in SOT Patients up to 30 weeks of study participation Analysis all stool samples and compare the effects of FMT and oral vancomycin on intestinal colonization with multi-drug resistant organisms (other than C. difficile) in SOT patients
Trial Locations
- Locations (5)
Northwestern University
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Wisconsin Hospital & Clinics
🇺🇸Madison, Wisconsin, United States
Northwestern University🇺🇸Chicago, Illinois, United States