Faecal Microbiota Transplantation in Irritable Bowel Syndrome (MISCEAT)

Faecal Microbiota Transplantation in Irritable Bowel Syndrome: a Randomised, Double-blind Cross-over Study Utilising Mixed Microbiota From Healthy Donors

Irritable bowel syndrome (IBS) is the most common functional bowel disorder, being present in approximately 10% of adult Europoid population. The etiology of IBS is elusive. Literature indicates that modification of patients´colonic microbiota might ameliorate the condition. Here we test an intervention by faecal microbiota transplantation of artificially inflated microbiome diversity, versus autoclaved placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Irritable Bowel Syndrome With Diarrhea; Irritable Bowel Syndrome Mixed
• Intervention / Treatment: Other: Faecal microbiota transplantation with active study microbiota first; Other: Faecal microbiota transplantation with inactive autoclaved study microbiota first; Other: Faecal microbiota transplantation with inactive autoclaved study microbiota only

Detailed Description

Three-groups, double-blind, placebo-controlled, randomised, cross-over study in adult patients diagnosed with IBS (diarrhoeal or mixed form) according to Rome IV criteria. Each study subject will undergo two pairs of faecal microbiota transplantation (a total of four enemas for each patient), with the pairs of transfers being eight weeks apart. The active intervention substance is a mixed stool microbiota derived from healthy individuals, screened for infectious diseases according to European consensus conference on faecal microbiota transplantation guidelines, and who were preselected for high alpha diversity of their microbiome and distance in community ordination from IBS patients microbiota. Placebo is the same mixture, inactivated by autoclaving.

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 14059
    • Thomayer University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diarrhea Predominant Irritable Bowel Syndrome (IBS-D) or Irritable Bowel Syndrome with mixed bowel habits (IBS-M) according to the Rome IV criteria

Exclusion Criteria:

• The use of antibiotics within one month prior to faecal microbiota transplantation
• The use of probiotics within one month prior to faecal microbiota transplantation
• History of inflammatory bowel disease or gastrointestinal malignancy, systemic autoimmune diseases (ongoing or in history)
• Previous abdominal surgery (other than appendectomy or cholecystectomy or hernioplasty or cesarean section)
• HIV infection or other active infection
• Renal or hepatic disease (both defined by biochemistry workup)
• Diabetes mellitus, abnormal thyroid functions not controlled by thyroid medications
• Bipolar disorder or schizophrenia (ongoing or history thereof), moderately severe depression defined by Patient Health Questionnaire-9 (PHQ-9) score > 15
• Anxiety defined by a Generalised Anxiety Disorder 7 (GAD7) score > 10
• Current pregnancy and lactation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A (active microbiota first); Patients will first receive two enemas of active study microbiota mixture (deep-frozen stored stool microbiota mixed from eight donors in order to increase its diversity), then after eight weeks they will receive two enemas with placebo.	Other: Faecal microbiota transplantation with active study microbiota first; 2x enema with active study microbiota; after 8 wks 2x enema with inactive autoclaved study microbiota
Other: Group B (inactive microbiota first); Patients will first receive placebo, then the active study microbiota mixture.	Other: Faecal microbiota transplantation with inactive autoclaved study microbiota first; 2x enema with inactive autoclaved study microbiota; after 8 wks 2x enema with active study microbiota
Other: Group C (inactive microbiota only); Patients will receive similarly timed enemas with placebos only.	Other: Faecal microbiota transplantation with inactive autoclaved study microbiota only; 2x enema with inactive autoclaved study microbiota; after 8 wks 2x enema with inactive autoclaved study microbiota

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the IBS severity symptom score (IBS-SSS)	Change in the IBS severity symptom score (IBS-SSS) in the active microbiota group relative to the placebo group.	The difference between the score at four weeks after the intervention (study weeks 5 or 13, respectively) and the baseline score (week -1 in 'Active microbiota first' group or week 8 in 'Inactive microbiota first' group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The acute change in the IBS severity symptom score (IBS-SSS)	IBS-SSS between baseline and two weeks after intervention	study weeks 3 and 11, respectively
The long-term change in the IBS severity symptom score (IBS-SSS)	IBS-SSS between baseline (week -1) and week 32. The long term change will compare placebo group to merged active study microbiota groups.	baseline and study week 32
Change in number of loose stools per day	Change in number of loose stools per day in the active microbiota group relative to the placebo group	baseline and study week 32
Change in stool consistency	Change in stool consistency evaluated by Bristol stool scale (type 3 and 4 - normal; types 1,2,5,6 and 7 - abnormal) in the active microbiota group relative to the placebo group	baseline and study week 32
Change in abdominal pain	Change in abdominal pain measured by Visual Analogue Scale (VAS) (0 - no pain, 10 - worst pain) in the active microbiota group relative to the placebo group	baseline and study week 32
Change in frequency of bloating per week	Change in frequency of bloating per week (as there is no standardised measurement, it will be reported as number of episodes per time unit, where the possible answers could be: no bloating, bloating once a week, twice a week, three times a week, four times a week, five times a week, six times a week, bloating daily, bloating daily and sometimes at night, bloating more than half of days, bloating continuously) in the active microbiota group relative to the placebo group	baseline and study week 32
Change in Body Mass Index	Change in Body Mass Index (BMI in kg/m^2) in the active microbiota group relative to the placebo group	baseline and study week 32
Change in waist circumference	Change in waist circumference (in centimeters) in the active microbiota group relative to the placebo group	baseline and study week 32
Change in body fat mass estimated by skinfold thickness measuring	Change in body fat mass estimated by measuring combined skinfold thickness at given locations (biceps, triceps, subscapular, suprailiac) in millimetres in the active microbiota group relative to the placebo group	baseline and study week 32
Change in body fat mass measured by bioelectrical impedance analysis	Change in body fat mass in the active microbiota group relative to the placebo group measured by bioelectrical impedance analysis (in %)	baseline and study week 32
Change in faecal microbiome's alpha (within-sample) diversity	Change in faecal microbiome's alpha (within-sample) diversity in the active microbiota group relative to the placebo group measured by Chao index of alpha diversity (higher value means higher alpha-diversity)	baseline and study week 32
Change in faecal microbiome's beta (between samples) diversity	Change in faecal microbiome's beta (between samples) diversity in the active microbiota group relative to the placebo group assessed by the quantitative Bray-Curtis index (more distant means more different bacterial composition) ordinated by nonmetric multidimensional scaling (NMDS)	baseline and study week 32
Change in the quantity of single-cell protist Blastocystis	Change in the quantity of single-cell protist Blastocystis in the active microbiota group relative to the placebo group assessed by a specific quantitative polymerase chain reaction assay measured in genomic equivalents per microlitre DNA (the higher concentration means more of Blastocystis)	baseline and study week 32
The psychological and well-being effects of the therapy (IBS-QoL)	The psychological and well-being effects of the therapy scored by IBS-QoL questionnaires	baseline and study week 32

Collaborators and Investigators

• Sponsor: Thomayer University Hospital
• Collaborators: Charles University, Czech Republic
• Investigators: Principal Investigator: Pavel Kohout, Thomayer University Hospital, Prague, Czech Republic

Publications and helpful links

General Publications

• Hurych J, Vejmelka J, Hlinakova L, Kramna L, Larionov V, Kulich M, Cinek O, Kohout P. Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors. BMJ Open. 2022 Jun 27;12(6):e056594. doi: 10.1136/bmjopen-2021-056594.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: IBS - D, IBS - M
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: INT_TN_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only the researchers involved in the study have access to the final study dataset (IBS-SSS, frequency of urgent defecations, Bristol stool scale, abdominal pain and bloating), which will be shared in an anonymised form via the Zenodo repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No