FMT in Initial CDI

Study Overview
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Brief Summary
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The study explores fecal microbiota transfer via retention enema after the first clostridioides difficile episode.

Detailed Description
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Clostridioides difficile infections (CDI) remain a significant burden for the patients and the society. According to the National Institute for Health and Welfare (THL), in 2018 there were 4324 CDIs in Finland. C. difficile typically affects patients whose gut microbiota is profoundly damaged by antibiotics. Standard therapy for CDI is antibiotic such as vancomycin. After the standard therapy gut microbiota remains damaged and vulnerable to C difficile reinfection arising from spores that survived the treatment. Early recurrence of CDI is commonly defined as relapse of symptoms and positive testing for fecal C difficile within three months after the previous episode. Recurrent CDI is reported in 10-30% of patients after initial treatment, with recurrence approaching 60% after the third episode. Fecal microbiota transplantation (FMT) is currently the most effective treatment for recurrent CDI (rCDI), with efficacy of over 90%. Even though FMT is mostly administered endoscopically, it is considered a cost-effective way to treat rCDI patients. FMT is recommended after the second relapse, in other words, after the third antibiotic course for CDI. FMT is most effective in rCDI when administered via colonoscopy. However, colonoscopy is a costly and invasive procedure. The largest study exploring a simple and inexpensive retention enema FMT for rCDI showed a 62% clinical response following a single FMT, and 85% after the second. Baro et al. found that FMT via enema was the most cost-effective initial strategy for the management of second recurrence of community-onset CDI. In the controlled FMT trials the adverse events have been similar with placebo. Also, the long term safety in up to four years follow up seems to be good. The patients treated with FMT seem to normalize their bowel symptoms faster compared to CDI patients treated with only antibiotics. FMT reduces antibiotic resistance genes in gut microbiota and therefore has a theoretical potential to reduce infections caused by multi-resistant organisms. A balanced gut microbiota is important in infection control and essential to normal bowel function. CDI is an indicator of damaged gut microbiota. After a course of antibiotics, the gut microbiota typically becomes less diverse for at least some months. It is not known whether the gut microbiota ever regains its former constitution after such a treatment. We hypothesize that planting a new microbial population soon after antibiotic treatment for CDI reduces the risk of recurrence as well as post-infectious functional bowel disorders. FMT via colonoscopy is currently recommended after the third CDI (second relapse). Our study explores FMT via inexpensive and minimally invasive retention enema after the first CDI episode.

Official Title
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Fecal Microbiota Transplantation in Initial Clostridioides Difficile Enteritis: a Randomized, Placebo-controlled Trial

Conditions
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Clostridioides Difficile Infection

Intervention / Treatment
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* Other: FMT
* Other: placebo enema


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years C. difficile PCR in feces positive and clinical symptoms of enteritis. Full resolution of diarrhea during antibiotic treatment for C. difficile No other ongoing antibacterial treatments. No ongoing probiotics. Signed informed consent. Exclusion Criteria: Pregnant Ongoing need for antibacterial treatment Life expectancy < 1 year Prior C. difficile infection in preceding 3 months Unable to provide written consent, due to dementia for example. Fecal incontinence i.e. inability to retain enema.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FMT enema<br>FMT enema 3-5 days after standard antibiotic treatment | Other: FMT<br>* Fecal microbiota transfer from a healthy and tested volunteer<br>|
| Placebo Comparator: plasebo enema<br>placebo | Other: placebo enema<br>* colored water enema<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clostridioides difficile relapse rate |  | month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of gastrointestinal symptoms | Primary symptoms of clostridioides difficile infection | month 3 and 1 year | 
| composition of fecal microbiota | Characterization of fecal microbiome samples down to species level by polymerase chain reaction (PCR) | month 3 and 1 year | 
| Retention time, i.e. time from FMT to subsequent defecation |  | day 1 | 
| Fecal microbiota transfer adverse events | possibly transferred infections, complications of administration etc | within 1 year of administration | 
| Adherence to FMT |  | From recruitment until FMT administration. Up to 15 days | 
| Alterations in mood as measured by total score of BDI | 0 to >30 points with higher points meaning more severe depression | month 3 and 1 year | 
| Anxiety as measured by total score of GAD-7 | 0 to 21 points with higher points meaning more severe anxiety | month 3 and 1 year | 
| Quality of life as measured by 15D instrument |  | month 3 and 1 year | 
| clostridioides difficile relapse rate |  | 1 year |