Tag Archives: Fecal Microbiota Transplant Studies

Recurrent Clostridium difficile associated diarrhea (rCDAD) Research Study Begins Enrollment

A research consortium across multiple institutions has begun enrolling patients in a clinical trial examining whether fecal microbiota transplantation by enema is safe and effective in preventing recurrent Clostridium difficile-associated disease, according to a press release.

The researchers hope to enroll 162 volunteers aged 18 years or older who have had two or more episodes of C. difficile-associated disease (CDAD) within the past 6 months, according to the release.

Trial sites include Emory University, Duke University Medical Center and Vanderbilt University Medical Center.

Each site is a member of the Vaccine and Treatment Evaluation Unit, which is a network funded by the National Institute of Allergy and Infectious Diseases (NIAID).

The researchers hope to enroll 162 volunteers aged 18 years or older who have had two or more episodes of C. difficile-associated disease (CDAD) within the past 6 months, according to the release.

Clostridium difficile-associated disease, a significant problem in health care facilities, causes an estimated 15,000 deaths in the United States each year,” Anthony S. Fauci, MD, NIAID director, said in the release. “This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using fecal microbiota transplants by enema to cure C. diff infections.”

Volunteers will be enrolled in the trial after completing a standard course of antibiotics for a recurrent CDAD episode, presuming their diarrhea symptoms cease on treatment.

Participants will then be randomly assigned to either a group (n = 108) that will take an anti-diarrheal medication and receive a stool transplant (FMT) delivered by retention enema, or a group (n = 54) that will take an anti-diarrheal medication and receive a placebo solution delivered by retention enema.

The placebo is a saline solution that has been colored to mimic an active stool transplant product, to ensure that the study is partially blinded.

Researchers will collect stool and blood samples from participating at designated intervals for a year from the date of effective treatment for CDAD, or from the date of their last treatment if it was unsuccessful, according to the release.

Investigators will evaluate the stool samples for gut microbial diversity and infectious pathogens changes and will examine the blood samples for metabolic syndrome markers.

All participants will be monitored for adverse side effects for 3 years following the completion of recurrent CDAD treatment.

Source:  https://www.healio.com/gastroenterology/infection/news/online/%7B1402ede4-5de1-40a3-b23f-a0070e01ad7a%7D/trial-testing-fmt-for-recurrent-diarrheal-disease-begins

Fecal Microbiota Transplantation From A Donor To Treat Recurrent C.difficle Infection

Fecal microbiota transplantation (FMT) from a donor (heterologous) to treat recurrent Clostridium difficile infection (CDI) is safe and more effective than self (autologous) transplantation, according to data from a randomized controlled, double-blind clinical trial.

However, the results, published online August 23 in the Annals of Internal Medicine, also show that the treatment success rate in the control group varied substantially between two study locations, which suggests there are subtleties not yet understood with the approach.

The efficacy of FMT using donor stool to treat recurrent CDI has made headlines, but so far it has largely been tested only in open-label clinical trials and case series.

 

To complement these studies, Colleen R. Kelly, MD, from the Women’s Medicine Collaborative, The Miriam Hospital, Providence, Rhode Island, and coworkers enrolled 46 patients who had had at least three recurrences of CDI and who were treated with vancomycin for the most recent infection and randomly assigned them to receive donor or self stool preparations by colonoscopy.

The researchers assessed adverse events for 6 months after FMT, defining efficacy as cessation of diarrhea without the need for further antibiotics during the 8 weeks after the intervention. All stool was subject to microbiota analysis before and after FMT.

Twenty of the 22 patients in the donor FMT group (90.9%; 95% confidence interval [CI],69.2% – 97.8%) were clinically cured compared with

15 of the 24 (62.5%; 95% CI, 41.6% – 79.6%) patients who received self FMT (P = .042).

The nine patients who developed CDI after self FMT were then given donor FMT and were cured.

Microbiome analysis revealed no improvement in gut microbial diversity after self FMT, but restoration of a normal microbiota with donor FMT, including increases in Bacteroidetes and Firmicutes and decreases in Proteobacteria and Verrucomicrobia populations.

An unexpected finding was that patients treated autologously at Montefiore Medical Center in the Bronx, New York had a much higher cure rate than those treated autologously at The Miriam Hospital in Providence. Specifically, for Rhode Island, cure rate with donor FMT was 90.0% (CI, 51.8% – 98.7%) vs 42.9% (CI, 20.1% – 69.0%) with self FMT. For New York, cure rate with donor FMT was 91.7% (CI, 57.2% – 98.9%) compared with 90.0% (CI, 51.8% – 98.7%) with self FMT.

The researchers list clinical differences among the patients at the two sites that could explain the different responses to self FMT:

  • NY patients were infected longer, had more recurrences, and had more courses of fidaxomicin than did Rhode Island patients.
  • NY patients waited longer to be treated and took antibiotics longer before entering the study, and may have been cured at that time.
  • Fecal microbiomes among NY patients had more Clostridia species, which may have occupied niches for C difficile.

Limitations of the study include lack of inclusion of baseline antibody titers and infection severity, small sample size attributed partly to unwillingness of participants to risk assignment to the autologous group, and nonuniform stool doses. In addition, the researchers mention that some patients may be infected according to polymerase chain reaction (PCR)-based identification of the pathogen, but be asymptomatic, and that some patients may have diarrhea resulting from undiagnosed irritable bowel syndrome but also be infected with C difficile, according to PCR testing.

In an accompanying editorial, Elizabeth L. Hohmann, MD, from Massachusetts General Hospital in Boston, points out another limitation, that “the population enrolled in this trial was younger (mean age, 50 years) and seemed healthier and more adventurous than most patients with recurrent CDI.” In contrast, about 60% of her patients with whom she discusses FMT are older than 60 years, and 30% are older than 75 years. However, the investigators had to recruit patients younger than 75 years to comply with FDA regulations to consider FMT as an investigational new drug.

No serious adverse events were reported. The researchers conclude, “FMT using fresh donor stool administered via colonoscopy after a course of vancomycin was effective at preventing further CDI episodes in patients with multiply recurrent infection.” They call for additional investigation to identify types of patients most likely to benefit from FMT using donor stool.

Dr Hohmann regards the differing response rates to autologous FMT at the two study sites as instructive, underscoring the value of conducting a rigorous controlled trial even when the tested technology has proven itself in other types of investigations. “Their results prompt us to ask again whether microbial manipulation has any as-yet unappreciated health benefits or risks and whether there are preferred microbiomes for specific human populations or locales,” she concludes.

To read this article in its entirety:

http://www.medscape.com/viewarticle/867727?nlid=108986_2981&src=wnl_dne_160823_mscpedit&uac=206986BK&impID=1183588&faf=1