Clinical trial NCT04899869: Faecal Microbiota Transplantation in Irritable Bowel Syndrome
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
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome With Diarrhea
Irritable Bowel Syndrome Mixed
Keywords: IBS - D, IBS - M
Lead sponsor: Thomayer University Hospital
Sponsor class: OTHER
Collaborators: name: Charles University, Czech Republic
First posted: 2021-05-25
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in the IBS severity symptom score (IBS-SSS)
timeFrame: 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 outcomes:
measure: The acute change in the IBS severity symptom score (IBS-SSS)
timeFrame: study weeks 3 and 11, respectively
measure: The long-term change in the IBS severity symptom score (IBS-SSS)
timeFrame: baseline and study week 32
measure: Change in number of loose stools per day
timeFrame: baseline and study week 32
measure: Change in stool consistency
timeFrame: baseline and study week 32
measure: Change in abdominal pain
timeFrame: baseline and study week 32
measure: Change in frequency of bloating per week
timeFrame: baseline and study week 32
measure: Change in Body Mass Index
timeFrame: baseline and study week 32
measure: Change in waist circumference
timeFrame: baseline and study week 32
measure: Change in body fat mass estimated by skinfold thickness measuring
timeFrame: baseline and study week 32
measure: Change in body fat mass measured by bioelectrical impedance analysis
timeFrame: baseline and study week 32
measure: Change in faecal microbiome's alpha (within-sample) diversity
timeFrame: baseline and study week 32
measure: Change in faecal microbiome's beta (between samples) diversity
timeFrame: baseline and study week 32
measure: Change in the quantity of single-cell protist Blastocystis
timeFrame: baseline and study week 32
measure: The psychological and well-being effects of the therapy (IBS-QoL)
timeFrame: baseline and study week 32
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Thomayer University Hospital
Study officials:
affiliation: Thomayer University Hospital, Prague, Czech Republic
name: Pavel Kohout
role: PRINCIPAL_INVESTIGATOR
References:
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.