A Prospective Trial of Lyophilized Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection

Clostridium Difficile Infection Clinical Trial

Official title:

Prospective, Open-label Trial to Evaluate Efficacy of Lyophilized Fecal Microbiota Transplantation for Treatment of Recurrent C. Difficile Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592343
• Other study ID #: CDI.LYO.FMT.1
• Status: Completed
• Phase: Phase 2
• Start date: January 2016
• Est. completion date: January 2020

Study information

• Verified date: September 2020
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary goal is to study patients with recurrent Clostridium difficile Infection (CDI) treated with lyophilized Fecal Microbiota Transplantation (FMT) in an open-labelled controlled trial. The treatment failure rate will be evaluated as defined by the persistence of diarrhea and a positive C. difficile toxin assay. The safety, clinical response, and relapse rate in patients will be assessed.

Description:

Recurrence of CDI following a course of standard antibiotic therapy is high, especially in the elderly patients over 65 years of age, in hospitalized and in the immunocompromised patients. As CDI is characterized by intestinal dysbiosis. Fecal Microbiology Transplantation (FMT) has been investigated as alternative treatment for CDI and has been determined to be effective and safe. One of the major challenges of offering FMT is the availability of suitable donors. A donor may no longer be able to continue to donate for a number of reasons and this may lead to temporary interruption of FMT in centers which offer the program. In order to continue to offer FMT whenever needed, we will investigate the efficacy of lyophilized FMT. The lyophilization (freeze-drying) process works by dehydrating a frozen donor stool sample to complete dryness, using controlled temperature and pressure gradients. This lyophilized process results in a powdered form of the sample. Studies have shown that lyophilized donor stool samples have similar microbial compositions as the same fresh sample.The technique of freeze drying has been used for decades for the industrial storage of microbes and has been used. Preliminary study of lyophilized stool for FMT has been performed in dogs. Preliminary efficacy data in dogs with inflammatory bowel disease suggest equal efficacy as compared to fresh stool, although controlled study has yet to be performed. Should the lyophilized FMT (L-FMT) demonstrate to be equally or more effective than frozen FMT, there would be significant advantages. As with frozen FMT, lyophilized FMT will allow patients to receive FMT immediately as it can take up to two weeks for a donor's screening laboratory testing results to be available. Lyophilized FMT will also be more cost effective as less number of donors will need to be screened given the prolonged shelf life of lyophilized FMT which can be kept at above the freezing temperature. 9 This will also allow wider distribution and accessibility especially to the regions with limited capacity to manufacture FMT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• • Age 18 years or older.

• Able to provide informed consent.

• Willing and able to comply with all the required study procedures.

• A positive stool test for C. difficile toxin/gene using either PCR or enzyme immunoassay within 3 months of recruitment.

• History of at least = 2 recurrent CDI within 180 days where recurrence is de?ned as return of diarrhea consistent with CDI within 8 weeks following CDI symptom resolution for at least 24 hours after a minimum of 10-day course of standard antibiotic therapy for each episode and/or ongoing symptoms consistent with CDI* (defined below) despite at least 7 days of treatment using oral vancomycin at a minimum dose of 250 mg po four times daily.

*Symptoms of CDI include: diarrhea de?ned as: 3 or more unformed bowel movements in 24 hours for a minimum of 2 days with no other causes for diarrhea

• Receiving at least 7 days of antibiotic to control current episode of CDI

Patient exclusion criteria

• Planned or actively taking another investigational product

• CDI symptom-free for 3 or more weeks following completion of CDI treatment

• Patients with neutropenia with absolute neutrophil count <0.5 x 109/L

• Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray

• Peripheral white blood cell count > 30.0 x 109/L AND temperature > 38.0 ºC

• Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or Campylobacter.

• Presence of colostomy

• Unable to tolerate FMT or enema for any reason.

• Requiring systemic antibiotic therapy for more than 7 days.

• Actively taking Saccharomyces boulardii or other probiotic; yogurt is allowed

• Severe underlying disease such that the patient is not expected to survive for at least 30 days.

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Enterocolitis, Pseudomembranous
• Infection

Intervention

Biological:
• Lyophilized Fecal Microbiota Transplantation

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Sunnybrook Health Sciences	Toronto	Ontario
Canada	Royal Jubilee Hospital	Victoria	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of lyophilized fecal microbiota transplantation (FMT) for treatment of recurrent C. difficile infection	Evaluate treatment efficacy as determined by no recurrence of CDI-related diarrhea at 13 weeks after receiving up to 2 lyophilized FMTs without the need for an intervention (antibiotics or FMT) specifically for recurrence of CDI.	13 weeks from last FMT
Secondary	Recurrence of CDI following lyophilized fecal microbiota transplantation (FMT)	Evaluate treatment failure rate as defined by persistence of diarrhea and a positive C. difficile toxin assay or tcdB PCR within 5 days of the last FMT, or the need for additional intervention for CDI, colectomy or death directly due to CDI at 13 weeks following the last FMT.	13 weeks from last FMT
Secondary	Evaluate safety based on the number of patients with grade 3 to grade 5 adverse events related to lyophilized fecal microbiota transplantation (FMT)	Grade NCI common terminology criteria for adverse events, version 4.0 on a five-point scale. Grade 1 - 5: mild, moderate, severe, life-threatening or death	13 weeks from last FMT