Irritable Bowel Syndrome Mixed, Irritable Bowel Syndrome With Diarrhea
Conditions
Keywords
IBS - D, IBS - M
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.
Interventions
OTHERFaecal microbiota transplantation with active study microbiota first
2x enema with active study microbiota; after 8 wks 2x enema with inactive autoclaved study microbiota
OTHERFaecal microbiota transplantation with inactive autoclaved study microbiota first
2x enema with inactive autoclaved study microbiota; after 8 wks 2x enema with active study microbiota
OTHERFaecal 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
Sponsors
Charles University, Czech Republic
Thomayer University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
double-blind
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the IBS severity symptom score (IBS-SSS) | 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) | Change in the IBS severity symptom score (IBS-SSS) in the active microbiota group relative to the placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The long-term change in the IBS severity symptom score (IBS-SSS) | baseline and study week 32 | 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 | baseline and study week 32 | Change in number of loose stools per day in the active microbiota group relative to the placebo group |
| Change in stool consistency | baseline and study week 32 | 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 | baseline and study week 32 | 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 | baseline and study week 32 | 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 | baseline and study week 32 | Change in Body Mass Index (BMI in kg/m\^2) in the active microbiota group relative to the placebo group |
| The acute change in the IBS severity symptom score (IBS-SSS) | study weeks 3 and 11, respectively | IBS-SSS between baseline and two weeks after intervention |
| Change in body fat mass estimated by skinfold thickness measuring | baseline and study week 32 | 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 | baseline and study week 32 | 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 | baseline and study week 32 | 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 | baseline and study week 32 | 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 | baseline and study week 32 | 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) | baseline and study week 32 | The psychological and well-being effects of the therapy scored by IBS-QoL questionnaires |
| Change in waist circumference | baseline and study week 32 | Change in waist circumference (in centimeters) in the active microbiota group relative to the placebo group |
Countries
Czechia
Outcome results
None listed