FMT in Patients With Recurrent CDI and Ulcerative Colitis: Single Infusion Versus Sequential Approach

NCT ID: NCT06071312

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-23
• Study Completion Date: 2025-09-24

Brief Summary

Clostridioides difficile infection (CDI) is the most frequent cause of infectious diarrhea in hospitalized patients and is responsible for 20-30 % of antibiotic-associated diarrhea cases. Inflammatory bowel diseases (IBD) are associated with an higher prevalence, recurrence and severity of CDI. The prevalence of recurrent CDI in patients with IBD is 2.5 to 8 times higher than in the general population, with a cumulative lifetime risk of 10 %. The higher risk to the development of CDI in patient with IBD is directly related to the microbiome alterations that are associated with this chronic disoder. Moreover, the use of antibiotics to cure CDI further worsens the gut microbiota, triggering potentially a self-maintaining cycle and predisposes such patients to a higher risk of recurrence. In these patients, CD superinfection is associated, with an increased rate of hospitalization, length of stay, the need to modify the treatment to the underlying disease, the increase rate of colectomy, there higher mortality rate, with a net increase of health costs.

Nowadays, as emerged by several studies FMT has been established as a valid treatment option against recurrent CDI (rCDI), and it is recommended by international guidelines.

Unfortunately, most FMT studies for rCDI have excluded patients with IBD. Recent evidence suggests that FMT is effective in patients with ulcerative colitis (UC) and concomitant rCDI, both in the treatment of the infection and in the improve of disease activity. To date, most studies evaluated the efficacy of single infusion of FMT in these patients.

Preliminary data from our group suggest that a sequential approach (i.e., repeated fecal infusions) may increase the efficacy of FMT in this population. Indeed, in 18 patients with IBD, single infusion fecal resulted in eradication of rCDI in 60% of cases, whereas this outcome was achieved in 89% of cases using a sequential approach. Similar data have been demonstrated in a retrospective study by Fischer and colleagues. However, more studies are advocated to confirm these results.

Therefore, our study aim to compare the efficacy of single FMT vs. sequential in the eradication of rCDI in patients with UC.

Detailed Description

Clostridioides difficile infection (CDI) is the most frequent cause of infectious diarrhea in hospitalized patients and is responsible for 20-30 % of antibiotic-associated diarrhea cases. Inflammatory bowel diseases (IBD) are associated with an higher prevalence, recurrence and severity of CDI. The prevalence of recurrent CDI in patients with IBD is 2.5 to 8 times higher than in the general population, with a cumulative lifetime risk of 10 %. The higher risk to the development of CDI in patient with IBD is directly related to the microbiome alterations that are associated with this chronic disoder. Moreover, the use of antibiotics to cure CDI further worsens the gut microbiota, triggering potentially a self-maintaining cycle and predisposes such patients to a higher risk of recurrence. In these patients, CD superinfection is associated, with an increased rate of hospitalization, length of stay, the need to modify the treatment to the underlying disease, the increase rate of colectomy, there higher mortality rate, with a net increase of health costs.

Nowadays, as emerged by several studies FMT has been established as a valid treatment option against recurrent CDI (rCDI), and it is recommended by international guidelines.

Unfortunately, most FMT studies for rCDI have excluded patients with IBD. Recent evidence suggests that FMT is effective in patients with ulcerative colitis (UC) and concomitant rCDI, both in the treatment of the infection and in the improve of disease activity. To date, most studies evaluated the efficacy of single infusion of FMT in these patients.

Preliminary data from our group suggest that a sequential approach (i.e., repeated fecal infusions) may increase the efficacy of FMT in this population. Indeed, in 18 patients with IBD, single infusion fecal resulted in eradication of rCDI in 60% of cases, whereas this outcome was achieved in 89% of cases using a sequential approach. Similar data have been demonstrated in a retrospective study by Fischer and colleagues. However, more studies are advocated to confirm these results.

Therefore, our study aim to compare the efficacy of single FMT vs. sequential in the eradication of rCDI in patients with UC.

The extended aims of our study are:

• To compare the efficacy of single FMT versus sequential FMT in eradicating rCDI in patients with UC at 8 weeks after the end of treatment.
• To compare the efficacy of single FMT versus sequential FMT in the eradication of rCDI in patients with UC in the short term (1-4 weeks after the end of treatment).
• To evaluate the safety of the two treatments.
• To evaluate any changes in the microbiota following treatment.
• To assess disease activity of UC by clinical scores (partial Mayo score) at 8 weeks.

The investigators will carry out a randomized, controlled, open-label, single-clinical trial of single FMT vs sequential FMT in patients with active UC with concomitant rCDI, will be recruited among those referred to the gastroenterology unit of the Fondazione Policlinico Universitario "A. Gemelli". Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study.

Before randomization, demographic data will be collected by the gastroenterology staff.

Moreover, patients will be requested to give stool samples to be collected in a sterile, sealed container and stored at -80°C for metagenomic assessment of gut microbiome by the microbiology staff.

After baseline assessments, patients will be randomly assigned to one of the following treatment arms:

• Single FMT (Si-FMT);
• Sequential FMT (Se-FMT), consisting of 3 fecal infusions, each 3-6 days apart, within 18 days after randomization.

Each patient will undergo FMT procedure through colonoscopy under sedation; Fecal infusates will be delivered through the operative of the colonoscope, using 50-mL syringes.

Patients in the Si-FMT and Se-FMT arms will receive frozen feces from a healthy non related donor following the protocols suggested by the international guidelines. Patients in the Se-FMT arm will receive frozen feces from the same donor.

The selection of stool donors will be performed by the gastroenterology staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganization of fecal microbiota transplant during the COVID-19 pandemic.

The assignment of fecal infusates from healthy donors to patients will be done randomly, without any specific recipient- donor match, as this is not recommended by international guidelines All fecal infusates will be manufactured in the microbiology unit of our hospital. Only frozen feces will be used. Preparation of frozen feces will follow protocols from international guidelines.

Follow-up visits will be performed by physicians from the gastroenterology unit. All patients will be followed up for 2 months after the end of treatments. Follow- up visits will be scheduled at week 1, week 4, and week 8, after the end of treatments.

At each visit the following assessments will be performed: 1) collection of a stool sample for C. difficile toxin evaluation; 2) collection of a stool sample for metagenomic analysis of the gut microbiota; 3) clinical evaluation of disease activity; and 4) recording of adverse events.

Study Outcomes are detailed in the specific section of this website.

The statistical analysis will be performed both on an intention-to-treat and per- protocol basis. Differences among groups will be assessed with a two tailed Wilcoxon-rank sum test for continuous data and with Fisher's exact probability test (using two-tailed P-values) for categorical data. Differences in cure percentages will be determined with Fisher's exact test (with two-tailed P values). Microbiome analysis will be performed with shotgun sequencing techniques. For microbiome analysis statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through the R statistical software package (R Core Team, Vienna, Austria).

Conditions

Clostridium Difficile; Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

. Single FMT

Patients enrolled in this arm will receive a single infusion of donor FMT

Group Type: EXPERIMENTAL

single FMT

Intervention Type: BIOLOGICAL

This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through a single infusion of FMT

Sequential FMT

Patients enrolled in this arm will receive sequential infusions of donor FMT

Group Type: ACTIVE_COMPARATOR

sequential FMT

Intervention Type: BIOLOGICAL

This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through multiple infusions of FMT (sequential approach)

Interventions

single FMT

This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through a single infusion of FMT

Intervention Type: BIOLOGICAL

sequential FMT

This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through multiple infusions of FMT (sequential approach)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years;
• Active UC (partial Mayo score ≥2);
• Relapsing infection of C. difficile;
• Ability to express consent for inclusion in the study.
• Indication, in the clinical practice setting, for fecal microbiota transplantation from a healthy donor for recurrent CDI

Exclusion Criteria

• Age < 18 years;
• Other gastrointestinal infections, excluding C. difficile;
• Known gastrointestinal diseases, other than UC, in active stage (e.g., infectious gastroenteritis, celiac disease, irritable bowel syndrome, chronic pancreatitis, bile acid diarrhea, etc.);
• Previous colon surgery or skin ostomy packing;
• Food allergies;
• Current or recent (<2 weeks) therapy with drugs that may alter the microbiota (e.g., systemic antimicrobials, probiotics, proton pump inhibitors, immunosuppressants, metformin), except antibiotics against C. difficile;
• Heart failure or heart disease with FE ≤ 30 %;
• Severe respiratory failure;
• Psychiatric disorders;
• Pregnancy and lactation;
• Inability to provide informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

IANIRO GIANLUCA

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gianluca Ianiro, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Digestive Disease Center, Fondazione Policlinico Univesitario A. Gemelli IRCCS

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gianluca Ianiro, MD

Role: CONTACT

gianluca.ianiro@unicatt.it

+39 0630157338

Serena Porcari, MD

Role: CONTACT

porcariserena89@gmail.com

+39 0630157338

Facility Contacts

Gianluca Ianiro, MD

Role: primary

gianluca.ianiro@hotmail.it

0630156265

Serena Porcari, MD

Role: backup

porcariserena89@gmail.com

Other Identifiers

5183

Identifier Type: -

Identifier Source: org_study_id