Clinical trial NCT05257538: FMT in Initial CDI
Official title: Fecal Microbiota Transplantation in Initial Clostridioides Difficile Enteritis: a Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Clostridioides Difficile Infection
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Satakunta Central Hospital
name: Helsinki University Central Hospital
name: PaijatHame Central Hospital
First posted: 2022-02-25
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study explores fecal microbiota transfer via retention enema after the first clostridioides difficile episode.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: clostridioides difficile relapse rate
timeFrame: month 3
Secondary outcomes:
measure: Resolution of gastrointestinal symptoms
timeFrame: month 3 and 1 year
measure: composition of fecal microbiota
timeFrame: month 3 and 1 year
measure: Retention time, i.e. time from FMT to subsequent defecation
timeFrame: day 1
measure: Fecal microbiota transfer adverse events
timeFrame: within 1 year of administration
measure: Adherence to FMT
timeFrame: From recruitment until FMT administration. Up to 15 days
measure: Alterations in mood as measured by total score of BDI
timeFrame: month 3 and 1 year
measure: Anxiety as measured by total score of GAD-7
timeFrame: month 3 and 1 year
measure: Quality of life as measured by 15D instrument
timeFrame: month 3 and 1 year
measure: clostridioides difficile relapse rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku University hospital
Study officials:
References: