Fecal Microbiota Therapy for Recurrent Clostridium Difficile Infection

Interventional, single arm, single-centre trial to evaluate the effectiveness and safety of fecal microbiota therapy (FMT) in the investigators population.

Study Overview

• Status: Unknown
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Biological: Fecal Microbiota; Drug: vancomycin; Drug: Loperamide; Drug: metronidazole

Detailed Description

This is a study of the effects of FMT for the treatment of patients with recurrent Clostridium difficile infection (CDI). The investigators plan to enrol approximately 5-10 patients per year over the next 5 years to a maximum of 50 patients. Patients with recurrent CDI referred to the designated Gastrointestinal (GI) or Infectious Diseases (ID) services will be screened for inclusion and exclusion by the primary investigator (PI), sub investigators and/or designated study personnel.

Those patients meeting the criteria will be offered FMT and will be the recipient. An informed consent will be obtained from both the recipient and the donor prior to proceeding with the study protocol. Demographic information as well as details of the medical history and results of standard laboratory tests will be collected on the recipients and donors.

The donor preferably should be < 60 years old to maximize the fecal microbiota. As this does involve biological samples there is a theoretical risk of transmission of an infectious agent. To minimize this risk, the donors will be selected preferentially from a spouse or sexual partner. If this is not possible, then another relative or acquaintance would serve as the donor as identified by the recipient. In either case, the donor will be screened for potentially transmissible infections. This will include a health screening questionnaire adapted from Canadian Blood Services, a clinical examination and laboratory investigations to rule out known transmissible infectious diseases. The donor will complete a satisfaction survey.

The submitted stool will be processed in the lab as per the "Stool Prep Protocol". The route of administration will be by retention enema via a rectal tube. As the treatment is not an emergency the investigators will have the option, if necessary, to store the stool for future treatment. If the sample is not used it will be discarded at 90 days and another sample will be obtained if still required.

Prior to the treatment the recipient will also submit a sample of stool. Along with this a portion of the donor sample will be stored in at -80 degrees C for future molecular tests to determine the diversity of the microbiota. This may be performed at a later date dependent on obtaining the necessary funding.

Recipients will be followed for 6 months post FMT to monitor for success of treatment, adverse reactions, recipient satisfaction and a quality of life assessment.

note: if laboratory testing for Clostridium difficile (CD) changes the new test will replace the cytotoxicity test.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ian R Davis, MD,FRCPC; Phone Number: 902 473 8477; Email: ian.davis@nshealth.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults aged ≥ 18 yrs of age.
2. Recurrent CDI despite two courses of standard treatment (ie. 10 days of oral vancomycin or metronidazole) and a 6 week taper of oral vancomycin.
3. Laboratory confirmation of CDI by enzyme immunoassay (EIA), cytotoxicity assay and/or polymerase chain reaction (PCR).
4. Presence of persistent diarrhea defined as ≥ 3 loose or watery bowel movements in 24hr continuing for >2 days and diarrhea ongoing at the time of inclusion.

Exclusion Criteria:

1. Severely immunosuppressed patients will not be enrolled. This is defined as >20 mg prednisone/d for >1 month, recent transplant patients (haematological <2yrs and solid organ < 6 months), transplant with active graft versus host disease, HIV (with CD4<200), immunosuppressive antibody treatment (eg. tumour necrosis factor inhibitor, rituximab), other high dose long term systemic immunosuppression) and severe congenital immunodeficiency.
2. Age <18 years old.
3. Pregnancy.
4. Patient expected to expire in < 30d.
5. Current hospital admission for an indication other than CDI or need for vasopressor medication.

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: Fecal Microbiota Therapy; Vancomycin 125 mg po qid for 7 days or metronidazole 500 mg po tid for 7 days pre-treatment. Loperamide 4 mg po after morning prep and 2 mg post treatment. The route of administration fecal microbiota will be by retention enema via a rectal tube.

Biological: Fecal Microbiota; The fecal microbiota will be by retention enema administered through a rectal tube.; Drug: vancomycin; All subjects will be pre-treated with vancomycin 125 mg po qid X 7 days prior to the fecal microbiota.; Drug: Loperamide; The subject will take 4 mg of loperamide after the morning bowel prep (approximately 1 hour prior to the procedure) and 2 mg again after the procedure.; Drug: metronidazole; If unable to tolerate vancomycin, then it will be substituted with metronidazole 500 mg po tid X 7 days prior to the fecal microbiota.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of CDI	Resolution of CDI will be defined as < 3 bowel movements per day for 7 consecutive days or stool negative for Clostridium difficile (CD) on 2 consecutive stool sample at least 1 day apart within 30 days of the treatment.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success of treatment	Success of treatment with be absence of recurrence of CDI within 3 months of treatment. A recurrence will be defined as ≥ 3 bowel movements per day after a period of resolution with a positive stool for CD toxin within 3 months for treatment.	3 months
Adverse effects	Adverse effects experienced with treatment up to 6 months after treatment.	6 months
Quality of life	Quality of Life Assessment (prior to, 3 month and 6 months after FMT) using the Short Form 36 (SF-36) Health Survey.	day 0, 3 months and 6 months
Recipient Satisfaction	Recipient Satisfaction Survey which will be completed within 1 week of the FMT and again at 3 and 6 months post FMT.	1week, 3 months and 6 months
Donor Satisfaction	The donor will complete a satisfaction survey within 1 week after the stool donation.	1 week

Collaborators and Investigators

• Sponsor: Queen Elizabeth II Health Sciences Centre
• Investigators: Principal Investigator: Ian R Davis, MD,FRCPC, Dalhousie University, Department of Medicine, Division Infectious Diseases

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: January 25, 2016
• First Submitted That Met QC Criteria: February 16, 2016
• First Posted (Estimate): February 19, 2016

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: September 26, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Vancomycin; Metronidazole; Loperamide; Antidiarrheals
• Other Study ID Numbers: NSHA REB File #: 1020563

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO