Changes in Recipients Gut Microbiota After Fecal Microbiota Transplantation

NCT ID: NCT05739825

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-13
• Study Completion Date: 2026-02-14

Brief Summary

Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea, and the most common health care-associated infectious disease in the United States, accounting for 15% of overall infections, nearly 30.000 deaths per year an estimated economic expense of $5 billion/year.

In the last decade, most of the burden related to CDI depends on recurrence CDI (rCDI) (3). rCDI is known to extend the hospitalization length, and to be associated with increased morbidity and mortality rates.

Furthermore, rCDI is often, more than primary infection, associated with life-threatening complications, including pseudomembranous colitis, toxic megacolon, shock, perforation, bloodstream infection (BSI), sepsis, caused by intestinal bacteria or fungi with a mortality rate nearly 50%, and death.

Fecal microbiota transplantation (FMT), defined as the infusion of feces from healthy donors to recipient with disorders associated to dysbiosis, is known to be a highly effective treatment option against CDI. FMT is also more effective than standard treatment with vancomycin and it is recommended by International Guidelines for treating multiple recurrence of CDI.

Despite the increasing body of evidence about the clinical efficacy of FMT for the treatment of rCDI, mechanisms for this clinical efficacy are also unknown.

Metagenomics analysis is known as a good option to examine gut microbiota and to estimate microbial diversity. The aim of this study is to evaluate changes in microbial composition in rCDI patients after FMT, using metagenomics analysis.

Detailed Description

Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea, and the most common health care-associated infectious disease in the United States, accounting for 15% of overall infections, nearly 30.000 deaths per year an estimated economic expense of $5 billion/year.

In the last decade, most of the burden related to CDI depends on recurrence CDI (rCDI) (3). rCDI is known to extend the hospitalization length, and to be associated with increased morbidity and mortality rates.

Furthermore, rCDI is often, more than primary infection, associated with life-threatening complications, including pseudomembranous colitis, toxic megacolon, shock, perforation, bloodstream infection (BSI), sepsis, caused by intestinal bacteria or fungi with a mortality rate nearly 50%, and death.

Fecal microbiota transplantation (FMT), defined as the infusion of feces from healthy donors to recipient with disorders associated to dysbiosis, is known to be a highly effective treatment option against CDI. FMT is also more effective than standard treatment with vancomycin and it is recommended by International Guidelines for treating multiple recurrence of CDI.

Despite the increasing body of evidence about the clinical efficacy of FMT for the treatment of rCDI, mechanisms for this clinical efficacy are also unknown.

Metagenomics analysis is known as a good option to examine gut microbiota and to estimate microbial diversity. The aim of this study is to evaluate changes in microbial composition in rCDI patients after FMT, using metagenomics analysis.

The investigators will carry out a single-center observational perspective study. Patients 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 FMT procedure, demographic data will be collected by the gastrointestinal disease 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 and meta-transcriptome assessment by the microbiology staff.

Patients, according to clinical practice, will receive FMT procedure by colonoscopy. Each patient of the study will receive faeces from one single donor without any specific recipient-donor match. The selection of stool donors will be performed by the gastroenterology unit staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic. All faecal infusates will be manufactured in the microbiology unit of our hospital. Only frozen faeces will be used. Preparation of frozen faeces 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 3 months after the end of treatments.

Follow-up visits will be scheduled at week 1, week 2, week 4, and week 12, after the end of treatments. At each visit investigators will collect stool samples for microbiome analysis.

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

Clostridioides Difficile Infection Recurrence

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

FMT from healthy donors

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Recurrent Clostridioides difficile infection
• Age between 18 and 90 years old
• Ability to provide written informed consent
• Ability to be compliant with the scheduled procedures

Exclusion Criteria

• Another known gastrointestinal infection apart from C. difficile infection

. Known active gastrointestinal disorders (e.g. infectious gastroenteritis, coeliac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhoea)

• Previous colorectal surgery or cutaneous stoma
• Current or recent (< 6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antimicrobials, probiotics)
• Decompensated heart failure or heart disease with ejection fraction lower than 30%
• Severe respiratory insufficiency
• Psychiatric disorders
• Pregnancy or breastfeeding
• Unable to give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

IANIRO GIANLUCA

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gianluca Ianiro

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gianluca Ianiro, MD, PhD

Role: CONTACT

gianluca.ianiro@unicatt.it

+390630157338

Serena Porcari, MD

Role: CONTACT

porcariserena89@gmail.com

+390630157338

Facility Contacts

Gianluca Ianiro, MD

Role: primary

gianluca.ianiro@unicatt.it

+39 0630157338

References

Miller BA, Chen LF, Sexton DJ, Anderson DJ. Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile Infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol. 2011 Apr;32(4):387-90. doi: 10.1086/659156.

Reference Type: BACKGROUND

PMID: 21460491 (View on PubMed)

Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S88-92. doi: 10.1093/cid/cis335.

Reference Type: BACKGROUND

PMID: 22752870 (View on PubMed)

Falcone M, Russo A, Iraci F, Carfagna P, Goldoni P, Vullo V, Venditti M. Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection. Antimicrob Agents Chemother. 2015 Oct 19;60(1):252-7. doi: 10.1128/AAC.01927-15. Print 2016 Jan.

Reference Type: BACKGROUND

PMID: 26482315 (View on PubMed)

Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma N, Iqbal TH. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017 Sep;46(5):479-493. doi: 10.1111/apt.14201. Epub 2017 Jul 14.

Reference Type: BACKGROUND

PMID: 28707337 (View on PubMed)

Cammarota G, Masucci L, Ianiro G, Bibbo S, Dinoi G, Costamagna G, Sanguinetti M, Gasbarrini A. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43. doi: 10.1111/apt.13144. Epub 2015 Mar 1.

Reference Type: BACKGROUND

PMID: 25728808 (View on PubMed)

Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; quiz 499. doi: 10.1038/ajg.2013.4. Epub 2013 Feb 26.

Reference Type: BACKGROUND

PMID: 23439232 (View on PubMed)

Debast SB, Bauer MP, Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014 Mar;20 Suppl 2:1-26. doi: 10.1111/1469-0691.12418.

Reference Type: BACKGROUND

PMID: 24118601 (View on PubMed)

Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Hogenauer C, Malfertheiner P, Mattila E, Milosavljevic T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017 Apr;66(4):569-580. doi: 10.1136/gutjnl-2016-313017. Epub 2017 Jan 13.

Reference Type: BACKGROUND

PMID: 28087657 (View on PubMed)

Other Identifiers

3555

Identifier Type: -

Identifier Source: org_study_id