Lyophilized Fecal Transplant vs Lyophilized Fecal Filtrate in Recurrent C Diff Infection

Study Overview
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Brief Summary
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Fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (RCDI) has traditionally been offered as fecal slurry administered by enema, nasogastric tube or endoscopy. Frozen oral capsules have also shown efficacy. The potential advantage of lyophilized FMT is the relative ease of manufacturing and storage compared with fecal slurry. Sterile fecal filtrate has previously been shown to prevent Clostridium difficile infection (CDI) recurrence, suggesting that live bacteria may not be needed. This study will compare lyophilized sterile fecal filtrate (LSFF) with lyophilized FMT (LFMT) in the treatment of recurrent Clostridium difficile infection (RCDI).

Detailed Description
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This prospective double blind randomized pilot study will enroll 40 subjects with recurrent Clostridium difficile infection in a 1:1 ratio to receive either LSFF or LFMT by capsules. Subjects will receive 15 capsules at week 0 and be assessed at Weeks 1, 4, 12 and 24. If treatment fails, subjects will be given open label LFMT from the same donor. If treatment fails again, another FMT will be offered and the form and route of FMT delivery will be at the discretion of the treating physician.

Official Title
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A Prospective Double Blind Randomized Pilot Study Comparing the Efficacy of Lyophilized Fecal Microbiota Transplantation (FMT) to Lyophilized Sterile Fecal Filtrate in the Management of Recurrent Clostridium Difficile Infection (CDI)

Conditions
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Enterocolitis, Recurrent Clostridium Difficile Infection

Intervention / Treatment
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* Biological: LFMT
* Biological: LSFF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least 3 episodes of recurrent CDI, with each episode defined as 3 or more unformed stools in 24 hours associated with positive Clostridium difficile toxin, each occurring within 3 months of each other. CDI under symptomatic control with 3 or fewer unformed stools in 24 hours for at least 2 consecutive days prior to treatment Ability to provide informed consent. Females and males must agree to use effective contraception for the duration of the study as applicable Exclusion Criteria: Complicated CDI defined as WBC >35, significant abdominal pain and distention, evidence of toxin megacolon or pseudomembraneous colitis, hypotension defined as systolic blood pressure <90 mmHg unresponsive to fluid resuscitation, end organ failure, or requiring admission to intensive care. Chronic diarrheal illness such as irritable bowel syndrome or inflammatory bowel disease unless under control or in remission of 3 months prior to enrollment. Taking or planning to take an investigational drug within 3 months of enrollment. Immunosuppression Chemotherapy or radiation therapy oropharyngeal or significant esophageal dysphagia Ileus or small bowel obstruction Subtotal colectomy Pregnancy or planning to become pregnant within 3 months of enrollment Breastfeeding or planning to breastfeed during the trial Active infection requiring antibiotic therapy. Life expectancy <6 months -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blind randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LFMT<br>Lyophilized fecal microbiota transplant capsules | Biological: LFMT<br>* Lyophilized fecal microbiota transplant<br>|
| Experimental: LSFF<br>Lyophilized sterile fecal filtrate capsules | Biological: LSFF<br>* Lyophilized sterile fecal filtrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of RCDI | Proportion of subjects without RCDI | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of RCDI | Proportion of subjects with sustained cure | 24 weeks | 
| Serious Adverse Events | Mortality directly attributable to CDI or treatment | 8 weeks | 
| Serious Adverse Events | Infection directly attributable to treatment | 8 weeks | 
| Minor Adverse Events | nausea | 1 week | 
| Minor Adverse Events | vomiting | 1 week | 
| Minor Adverse Events | abdominal pain | 1 week | 
| Difficulty in swallowing capsules | Reported by subjects as ranging between none, moderate or severe | 1 week |