FMT in Initial CDI (FinCDI)

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

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

Study Overview

• Status: Recruiting
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Other: FMT; Other: placebo enema

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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Teppo U Stenholm; Phone Number: 023130000; Email: teppo.stenholm@tyks.fi

Study Locations

• Finland
  • Turku, Finland
    • Recruiting
    • Turku University Hospital
    • Contact: Teppo Stenholm; Phone Number: 023130000; Email: teppo.stenholm@tyks.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Helsinki University Central Hospital; PaijatHame Central Hospital; Satakunta Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Clostridium Infections
• Other Study ID Numbers: T123/2021

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No