Clinical trial NCT03617445: Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients
Official title: Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Clostridium Difficile Infection Recurrence
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-08-06
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Compare the Rate of Recurrence of CDI in Solid Organ Transplant Recipients With FMT Compared With Oral Vancomycin
timeFrame: 60 consecutive days
Secondary outcomes:
measure: CDI-related Quality of Life (QOL) Compared Using Treatment and Time Interaction as Model Terms While Adjusting for Potential Confounders
timeFrame: Weeks 4, 29 weeks
measure: Compare the Change in Gut Microbiota and Evaluate Changes in Microbiota to Assess for Safety of FMT in Patients
timeFrame: up to 30 weeks of study participation
measure: Number of Patients Who Experienced Short or Medium Term Adverse Events
timeFrame: Up 30 weeks of study participation
measure: Compare the Effects of FMT and Oral Vancomycin on Intestinal Colonization by Multi-drug-resistant Organisms Other Than C. Difficile in SOT Patients
timeFrame: up to 30 weeks of study participation
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Nasia Safdar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: