Lyophilized Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection

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

The primary goal is to study participants with recurrent C. difficile infection (CDI) treated with lyophilized fecal microbiota transplantation (FMT). The safety, clinical response and relapse rate in patients will be assessed.

Study Overview

• Status: Unknown
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: Lyophilized Fecal Microbiota Transplantation

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 12 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 unless patient taking treatment specifically for CDI for more than 3 months.

• History of at least ≥ 2 recurrent CDI where recurrence is defined 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 four times daily.

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

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
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label Lyophilized Fecal Microbiota Transplantation; Eligible participants with history of recurrent or refractory CDI	Drug: Lyophilized Fecal Microbiota Transplantation; Lyophilized FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment of CDI	Evaluate treatment efficacy determined by no recurrence of CDI-related diarrhea	13 weeks from last FMT

Collaborators and Investigators

• Sponsor: Vancouver Island Health Authority
• Investigators: Principal Investigator: Christine Lee, MD, Vancouver Island Health Authority

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2016
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections
• Other Study ID Numbers: CDI.LYO.FMT (C2016-020)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No