Fecal Microbiota Transplantation to Relieve Symptoms of Irritable Bowel Syndrome Without Constipation (TRAMIR)

TRApianto di Microbiota Intestinale in Pazienti Affetti da Sindrome Dell'Intestino IRritabile Senza Stipsi: Studio Clinico Randomizzato Controllato in Singolo Centro

Irritable bowel syndrome (IBS) is a complex multifactorial functional disorder, whose pathophysiology is largely associated to an impairment of the intestinal microbiota composition, namely dysbiosis. Thus, the modulation of the gut microbiota has been proposed as a possible therapeutic strategy for IBS patients alongside with current available drugs. Fecal microbiota transplantation (FMT) is a promising strategy to restore intestinal eubiosis. In this randomised double-blind placebo-controlled trial patients diagnosed with IBS without constipation are assigned with 1:1 ratio to receive FMT from healthy donor or autologous FMT (placebo group) to assess the effectiveness of FMT on IBS symptoms and quality of life, to evaluate the safety of FMT among IBS patients and to estimate any change in the gut microbiota composition of IBS patients after the FMT.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Procedure: Fecal microbiota transplantation (FMT)

Detailed Description

Irritable bowel syndrome (IBS) is a common chronic functional disorder with a prevalence varying between 10 and 15%. IBS is characterized by recurrent chronic abdominal pain associated with altered defecation. Intestinal dysbiosis is thought to be one of the major drivers in IBS pathophysiology, since several studies have shown that there are substantial differences in microbial composition between IBS patients and healthy subjects. Moreover, the modulation of the gut microbiota in IBS patients seems a promising therapeutic approach, since a benefit on symptoms with certain antibiotics, probiotics, prebiotics, synbiotics and diet has been reported. Fecal microbiota transplantation (FMT) from healthy donors is generally considered a safe and well-tolerated procedure ant it is described to be capable of restoring eubiosis of the recipient in the long term. Recently, a certain effectiveness of FMT in ameliorating intestinal symptoms, psychological aspects and quality of life alongside with a restoration of eubiosis among IBS patients has been described. This is a prospective randomized double-blind placebo-controlled trial aimed at estimating the benefits of FMT among IBS patients without constipation. The assessment of the effectiveness on IBS symptoms and quality of life, the evaluation of the safety and the changes in the gut microbiota composition (performed with shotgun sequencing techniques) among IBS patients will be evaluated before after the FMT. 35 patients will be enrolled in 24 months. Recruited subjects will be randomized with 1:1 ratio to receive FMT from healthy donors or autologous FMT (placebo). The effectiveness of FMT in improving the IBS symptoms and IBS-related quality of life will be estimated with the IBS-SSS and IBS-QOL questionnaire, respectively, before FMT and after 30, 60, 90 and 365 days. Moreover, the frequency and form of evacuations according to the Bristol scale will be recorded at the same timepoints from diaries provided to the patients. Changes in gut microbiota composition will be estimated by comparing the composition of the faecal microbiota of the recipient before and 90 days after the FMT. The data will be evaluated using Intention-to-treat (ITT) statistical analysis and per-protocol (PP) analysis. Difference between the two groups will be calculated by two-tailed tests, Wilcoxon-Rank Sum Test for continuous variables and by the Fisher's exact probability test for categorical variables. The response rate to FMT will be evaluated by the Fisher's exact test. Adverse events will be assessed. The composition of the faecal microbiota of the recipient before and after the FMT will also be analysed and also compared with the healthy donor's one using the UniFrac method.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy
    • Recruiting
    • Giovanni Cammarota
    • Contact: Giovanni Cammarota; Phone Number: 06-30156265; Email: Giovanni.Cammarota@unicatt.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to express and give informed consent
• Age ≥ 18 years
• Diagnosis of diarrhoea-predominant or unclassified IBS, according to the Rome IV criteria
• Have performed a colonoscopy within the last 5 years that has ruled out intestinal diseases

Exclusion Criteria:

• Taking antibiotics or probiotics within the 8 weeks before the baseline visit
• Patients with chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis, indeterminate colitis or eosinophilic gastroenteritis), malignant neoplasms of the gastroenteric tract, celiac disease, diverticular disease
• Uncontrolled heart failure or severe heart disease with EF < 30%
• Severe respiratory failure
• Serious psychiatric conditions or psychological instability according to the clinician
• Contraindication to fecal microbiota transplantation (high risk of complications related to colonoscopy)
• Previous abdominal surgery on the gastroenteric tract (except cholecystectomy, appendectomy and other types of surgery not involving the digestive tract)
• Patients with cutaneous enterostomy
• Pregnancy or lactation
• Concurrent enrollment in other interventional experimental protocols
• Personality unstable or unable to adhere to protocol procedures
• Any clinical condition which, in the opinion of the investigators, may contraindicate enrollment in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT from healthy donor; Subjects receiving a single infusion FMT via colonoscopy from healthy donor	Procedure: Fecal microbiota transplantation (FMT); Single FMT infusion via colonoscopy
Placebo Comparator: Autologous FMT; Subjects receiving a single infusion autologous FMT via colonoscopy	Procedure: Fecal microbiota transplantation (FMT); Single FMT infusion via colonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improving IBS symptoms assessed with the IBS severity scoring system (IBS-SSS)	To assess the effectiveness of healthy donor FMT in improving the symptoms of IBS without constipation compared to autologous microbiota transplantation using the IBS-SSS (< 175: mild IBS; 175-300: moderate IBS; > 300: severe IBS)	365 days
Number and severity grade of adverse events after FMT	To assess the number and severity grade of adverse events occurred after FMT	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life related to IBS evaluated with the IBS Quality of Life (IBS-QOL) questionnaire	To assess the effectiveness of healthy donor gut microbiota transplantation in improving the quality of life of patients with IBS without constipation compared to autologous FMT using the IBS-QOL questionnaire (range: 34-170; lower scores indicate better IBS-QoL)	365 days
Engraftment of donor microbiota after FMT, evaluated through the 16s rRNA sequencing	Changes in the fecal microbiota of the recipients after FMT from healthy donor or autologous microbiota transplantation will be evaluated through the 16s rRNA sequencing and compared to the baseline condition	365 days

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

General Publications

• 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.
• 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.
• Ianiro G, Masucci L, Quaranta G, Simonelli C, Lopetuso LR, Sanguinetti M, Gasbarrini A, Cammarota G. Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions. Aliment Pharmacol Ther. 2018 Jul;48(2):152-159. doi: 10.1111/apt.14816. Epub 2018 May 30.
• Ianiro G, Valerio L, Masucci L, Pecere S, Bibbo S, Quaranta G, Posteraro B, Curro D, Sanguinetti M, Gasbarrini A, Cammarota G. Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study. Clin Microbiol Infect. 2017 May;23(5):337.e1-337.e3. doi: 10.1016/j.cmi.2016.12.025. Epub 2017 Jan 3.
• Cammarota G, Ianiro G, Magalini S, Gasbarrini A, Gui D. Decrease in Surgery for Clostridium difficile Infection After Starting a Program to Transplant Fecal Microbiota. Ann Intern Med. 2015 Sep 15;163(6):487-8. doi: 10.7326/L15-5139. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2021
• Primary Completion (Anticipated): March 23, 2024
• Study Completion (Anticipated): December 23, 2024

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Gut microbiota; Fecal microbiota transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: 4474

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