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

Primary Purpose

Clostridium Difficile, Ulcerative Colitis

Status
Recruiting
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
single FMT
sequential FMT
Sponsored by
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile focused on measuring Ulcerative Colitis, Clostridium difficile, Fecal microbiota transplantation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Digestive Disease Center, Fondazione Policlinico Univesitario A. Gemelli IRCCSRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

. Single FMT

Sequential FMT

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of UC patients who will obtain the eradication of rCDI 8 weeks after treatments (single FMT vs sequential FMT)
The investigators will compare the number of participants who will obtain the eradication of rCDI (assessed by C. difficile toxin exam) 8 weeks after treatments (single FMT vs sequential FMT)

Secondary Outcome Measures

Number of UC patients who will obtain the eradication of rCDI 1 - 4 weeks after treatments (single FMT vs sequential FMT)
The investigators will compare the number of participants who will obtain the eradication of rCDI (assessed by C. difficile toxin exam) 1 - 4 weeks after treatments (single FMT vs sequential FMT).
Evaluation of changes in recipients' microbiome after treatments, at each time point.
The investigators will evaluate the characteristics of recipients' microbiome, assessed by metagenomics analysis, 1,4 and 8 weeks days after treatments, compared to baseline and donors' microbiome.
Evaluation of Ulcerative Colitis activity
The investigators will evaluate the clinical characteristics of ulcerative colitis, assessed by partial Mayo score, 1,4 and 8 weeks after treatments.
Evaluation of the safety of the two treatments
The investigators will record any adverse events (mild to severe) reported by participants, after treatments at each timepont.

Full Information

First Posted
October 3, 2023
Last Updated
October 5, 2023
Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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1. Study Identification

Unique Protocol Identification Number
NCT06071312
Brief Title
FMT in Patients With Recurrent CDI and Ulcerative Colitis: Single Infusion Versus Sequential Approach
Official Title
Fecal Microbiota Transplantation in Patients With Recurrent Clostridioides Cifficile Infection and Ulcerative Colitis: Single Infusion Versus Sequential Approach
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 23, 2023 (Actual)
Primary Completion Date
September 24, 2025 (Anticipated)
Study Completion Date
September 24, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile, Ulcerative Colitis
Keywords
Ulcerative Colitis, Clostridium difficile, Fecal microbiota transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, controlled, open-label, single-center trial.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
. Single FMT
Arm Type
Experimental
Arm Description
Patients enrolled in this arm will receive a single infusion of donor FMT
Arm Title
Sequential FMT
Arm Type
Active Comparator
Arm Description
Patients enrolled in this arm will receive sequential infusions of donor FMT
Intervention Type
Biological
Intervention Name(s)
single FMT
Intervention Description
This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through a single infusion of FMT
Intervention Type
Biological
Intervention Name(s)
sequential FMT
Intervention Description
This intervention is represented by the administration, in the recipients' gut, of healthy donor microbiota through multiple infusions of FMT (sequential approach)
Primary Outcome Measure Information:
Title
Number of UC patients who will obtain the eradication of rCDI 8 weeks after treatments (single FMT vs sequential FMT)
Description
The investigators will compare the number of participants who will obtain the eradication of rCDI (assessed by C. difficile toxin exam) 8 weeks after treatments (single FMT vs sequential FMT)
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Number of UC patients who will obtain the eradication of rCDI 1 - 4 weeks after treatments (single FMT vs sequential FMT)
Description
The investigators will compare the number of participants who will obtain the eradication of rCDI (assessed by C. difficile toxin exam) 1 - 4 weeks after treatments (single FMT vs sequential FMT).
Time Frame
1 months
Title
Evaluation of changes in recipients' microbiome after treatments, at each time point.
Description
The investigators will evaluate the characteristics of recipients' microbiome, assessed by metagenomics analysis, 1,4 and 8 weeks days after treatments, compared to baseline and donors' microbiome.
Time Frame
2 months
Title
Evaluation of Ulcerative Colitis activity
Description
The investigators will evaluate the clinical characteristics of ulcerative colitis, assessed by partial Mayo score, 1,4 and 8 weeks after treatments.
Time Frame
2 months
Title
Evaluation of the safety of the two treatments
Description
The investigators will record any adverse events (mild to severe) reported by participants, after treatments at each timepont.
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gianluca Ianiro, MD
Phone
+39 0630157338
Email
gianluca.ianiro@unicatt.it
First Name & Middle Initial & Last Name or Official Title & Degree
Serena Porcari, MD
Phone
+39 0630157338
Email
porcariserena89@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gianluca Ianiro, MD
Organizational Affiliation
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Digestive Disease Center, Fondazione Policlinico Univesitario A. Gemelli IRCCS
City
Rome
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gianluca Ianiro, MD
Phone
0630156265
Email
gianluca.ianiro@hotmail.it
First Name & Middle Initial & Last Name & Degree
Serena Porcari, MD
Email
porcariserena89@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data will be available to other researchers
IPD Sharing Time Frame
data will be available after the completion of the study, for 5 years
IPD Sharing Access Criteria
Data will be given upon request to the PI

Learn more about this trial

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

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