search
Back to results

Faecal Microbiota Transplantation in Irritable Bowel Syndrome (MISCEAT)

Primary Purpose

Irritable Bowel Syndrome With Diarrhea, Irritable Bowel Syndrome Mixed

Status
Active
Phase
Not Applicable
Locations
Czechia
Study Type
Interventional
Intervention
Faecal microbiota transplantation with active study microbiota first
Faecal microbiota transplantation with inactive autoclaved study microbiota first
Faecal microbiota transplantation with inactive autoclaved study microbiota only
Sponsored by
Thomayer University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome With Diarrhea focused on measuring IBS - D, IBS - M

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Thomayer University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Group A (active microbiota first)

Group B (inactive microbiota first)

Group C (inactive microbiota only)

Arm Description

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.

Patients will first receive placebo, then the active study microbiota mixture.

Patients will receive similarly timed enemas with placebos only.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The acute change in the IBS severity symptom score (IBS-SSS)
IBS-SSS between baseline and two weeks after intervention
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.
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
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
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
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
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
Change in waist circumference
Change in waist circumference (in centimeters) in the active microbiota group relative to the placebo group
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
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 %)
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)
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)
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)
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

Full Information

First Posted
May 19, 2021
Last Updated
August 16, 2023
Sponsor
Thomayer University Hospital
Collaborators
Charles University, Czech Republic
search

1. Study Identification

Unique Protocol Identification Number
NCT04899869
Brief Title
Faecal Microbiota Transplantation in Irritable Bowel Syndrome
Acronym
MISCEAT
Official Title
Faecal Microbiota Transplantation in Irritable Bowel Syndrome: a Randomised, Double-blind Cross-over Study Utilising Mixed Microbiota From Healthy Donors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 17, 2021 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Thomayer University Hospital
Collaborators
Charles University, Czech Republic

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
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome With Diarrhea, Irritable Bowel Syndrome Mixed
Keywords
IBS - D, IBS - M

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Each study subject will undergo two pairs of faecal microbiota transplantation eight weeks apart (a total of four enemas for each patient). Our study design has several specific features: (a) Two consecutive transfers were designed to improve study microbiota engraftment. Before the first of every transfer pairs, the subjects will receive a reduced dose of oral polyethylene glycol for partial bowel preparation. (b) To help discern potential carry-over effects, a placebo-only group was included; this also enables us to assess long-term effects of the intervention. (c) The transferred microbiota is identical throughout the study, having been mixed beforehand, aliquoted and deep frozen. Its alpha diversity was artificially increased by mixing stools from several donors. (d) Placebo is made of the same mixture by careful autoclaving.
Masking
ParticipantCare ProviderInvestigator
Masking Description
double-blind
Allocation
Randomized
Enrollment
99 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A (active microbiota first)
Arm Type
Other
Arm Description
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.
Arm Title
Group B (inactive microbiota first)
Arm Type
Other
Arm Description
Patients will first receive placebo, then the active study microbiota mixture.
Arm Title
Group C (inactive microbiota only)
Arm Type
Other
Arm Description
Patients will receive similarly timed enemas with placebos only.
Intervention Type
Other
Intervention Name(s)
Faecal microbiota transplantation with active study microbiota first
Intervention Description
2x enema with active study microbiota; after 8 wks 2x enema with inactive autoclaved study microbiota
Intervention Type
Other
Intervention Name(s)
Faecal microbiota transplantation with inactive autoclaved study microbiota first
Intervention Description
2x enema with inactive autoclaved study microbiota; after 8 wks 2x enema with active study microbiota
Intervention Type
Other
Intervention Name(s)
Faecal microbiota transplantation with inactive autoclaved study microbiota only
Intervention Description
2x enema with inactive autoclaved study microbiota; after 8 wks 2x enema with inactive autoclaved study microbiota
Primary Outcome Measure Information:
Title
Change in the IBS severity symptom score (IBS-SSS)
Description
Change in the IBS severity symptom score (IBS-SSS) in the active microbiota group relative to the placebo group.
Time Frame
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 Measure Information:
Title
The acute change in the IBS severity symptom score (IBS-SSS)
Description
IBS-SSS between baseline and two weeks after intervention
Time Frame
study weeks 3 and 11, respectively
Title
The long-term change in the IBS severity symptom score (IBS-SSS)
Description
IBS-SSS between baseline (week -1) and week 32. The long term change will compare placebo group to merged active study microbiota groups.
Time Frame
baseline and study week 32
Title
Change in number of loose stools per day
Description
Change in number of loose stools per day in the active microbiota group relative to the placebo group
Time Frame
baseline and study week 32
Title
Change in stool consistency
Description
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
Time Frame
baseline and study week 32
Title
Change in abdominal pain
Description
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
Time Frame
baseline and study week 32
Title
Change in frequency of bloating per week
Description
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
Time Frame
baseline and study week 32
Title
Change in Body Mass Index
Description
Change in Body Mass Index (BMI in kg/m^2) in the active microbiota group relative to the placebo group
Time Frame
baseline and study week 32
Title
Change in waist circumference
Description
Change in waist circumference (in centimeters) in the active microbiota group relative to the placebo group
Time Frame
baseline and study week 32
Title
Change in body fat mass estimated by skinfold thickness measuring
Description
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
Time Frame
baseline and study week 32
Title
Change in body fat mass measured by bioelectrical impedance analysis
Description
Change in body fat mass in the active microbiota group relative to the placebo group measured by bioelectrical impedance analysis (in %)
Time Frame
baseline and study week 32
Title
Change in faecal microbiome's alpha (within-sample) diversity
Description
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)
Time Frame
baseline and study week 32
Title
Change in faecal microbiome's beta (between samples) diversity
Description
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)
Time Frame
baseline and study week 32
Title
Change in the quantity of single-cell protist Blastocystis
Description
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)
Time Frame
baseline and study week 32
Title
The psychological and well-being effects of the therapy (IBS-QoL)
Description
The psychological and well-being effects of the therapy scored by IBS-QoL questionnaires
Time Frame
baseline and study week 32

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pavel Kohout
Organizational Affiliation
Thomayer University Hospital, Prague, Czech Republic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomayer University Hospital
City
Prague
ZIP/Postal Code
14059
Country
Czechia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
35760542
Citation
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.
Results Reference
derived

Learn more about this trial

Faecal Microbiota Transplantation in Irritable Bowel Syndrome

We'll reach out to this number within 24 hrs