Enterocolitis, Recurrent Clostridium Difficile Infection
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALLFMT
Lyophilized fecal microbiota transplant
BIOLOGICALLSFF
Lyophilized sterile fecal filtrate
Sponsors
University of Alberta
Dina Kao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
LFMT and LSFF capsules appear identical. Randomization is performed by lab staff not involved in any aspect of treatment administration or care
Intervention model description
double blind randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. CDI under symptomatic control with 3 or fewer unformed stools in 24 hours for at least 2 consecutive days prior to treatment 3. Ability to provide informed consent. 4. Females and males must agree to use effective contraception for the duration of the study as applicable
Exclusion criteria
1. 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. 2. Chronic diarrheal illness such as irritable bowel syndrome or inflammatory bowel disease unless under control or in remission of 3 months prior to enrollment. 3. Taking or planning to take an investigational drug within 3 months of enrollment. 4. Immunosuppression 5. Chemotherapy or radiation therapy 6. oropharyngeal or significant esophageal dysphagia 7. Ileus or small bowel obstruction 8. Subtotal colectomy 9. Pregnancy or planning to become pregnant within 3 months of enrollment 10. Breastfeeding or planning to breastfeed during the trial 11. Active infection requiring antibiotic therapy. 12. Life expectancy \<6 months -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of RCDI | 8 weeks | Proportion of subjects without RCDI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of RCDI | 24 weeks | Proportion of subjects with sustained cure |
| Serious Adverse Events | 8 weeks | Mortality directly attributable to CDI or treatment |
| Minor Adverse Events | 1 week | nausea |
| Difficulty in swallowing capsules | 1 week | Reported by subjects as ranging between none, moderate or severe |
Countries
Canada
Outcome results
None listed