Multi Strain Probiotic Preparation in Patients With Irritable Bowel Syndrome

Study Overview
=================
Brief Summary
-----------------
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders characterized by recurrent abdominal pain associated with defecation or a change in bowel habits without any structural abnormalities. Despite extensive research, the pathogenesis of IBS has not been clearly elucidated yet. Recent studies have shown that disturbed gut microbiota may promote the development and maintenance of IBS. Significant changes in the microbial communities of healthy controls vs IBS patients have been reported in several studies. These findings promoted the research on probiotics for the treatment of IBS. Probiotics are live microorganisms which, when administered at the right dose, have a positive effect on human health. The currently published systemic reviews and meta-analyses of randomized clinical trials have indicated that probiotics have beneficial clinical effects and can help to reduce global and specific IBS symptoms significantly. However, the effect depends on the specific composition of the probiotic preparation, and some meta-analyzes indicate that multi-strain preparations are more effective than single-strain preparations. Therefore, further research is highly anticipated. The purpose of the current clinical trial is to assess the effectiveness of multi-strain probiotic preparation in patients with diarrhea predominant IBS (IBS-D).

Official Title
-----------------
The Effectiveness of Multi Strain Probiotic Preparation in Patients With Diarrhea Predominant Irritable Bowel Syndrome - Randomized Double Blide Placebo Controlled Study

Conditions
-----------------
Irritable Bowel Syndrome With Diarrhea, Effects of Probiotics

Intervention / Treatment
-----------------
* Dietary Supplement: Multi-strain probiotic mixture of four Bifidobacterium, five Lactobacillus and one Streptococcus species or placebo
* Dietary Supplement: Maltodextrin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diarrhea-predominant irritable bowel syndrome (IBS-D) at least moderate form of IBS-D assessed using IBS-SSS, i.e. with score >175 male and female subjects of Caucasian race age between 16 and 70 years (inclusive) good physical, medical and mental status estimated on the basis of the medical history and a general clinical examination results of laboratory tests (hematology, clinical chemistry, serology, and urinalysis) within the normal range of the local laboratory or considered non-clinically significant by the investigator patients who have provided freely their own written informed consent patients available for the whole study period patients who are able to follow strictly the instructions of the investigational team regarding the study procedures and to fulfil the requirements of the protocol the following medications are permitted during the course of the study, as long as they are used at a constant dosage and are commenced at least 1 month prior to study start: birth control pill, or depot intramuscular contraceptive preparation, estrogen-progesterone replacement therapy, L-thyroxine, low-dose antidepressants (up to 25 mg day of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor), low-dose antihypertensives in the diuretic, angiotensin-converting enzyme inhibitor or angiotensin II inhibitor classes patients are allowed to take spasmolytic drugs on an ad hoc basis Exclusion Criteria: other than IBD-D types of IBD mild type of IBS-D (<175 points in IBS-SSS scale) the use of probiotics within last three months the treatment with antibiotics within last three months a concurrent severe illness (malignancies, uncontrolled hypertension and diabetes mellitus, hepatic, renal or cardiac dysfunctions, serious neurological disorders, psychosis, respiratory disorders such as asthma, chronic obstructive pulmonary disease, hyper- or hypothyroidism) chronic bowel disorders other than IBS, including inflammatory bowel diseases, gastroenteritis, stomach and duodenal ulcers, celiac diseases; pregnancy or lactation diagnosed lactose intolerance the use of motility drugs or dietary fiber supplements within 2 weeks before study start plan to have surgery during the time of the study a history of alcohol or drug abuse taking anti-coagulant medications participation in another clinical trial within last three months patients who will receive antibiotics during the study

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic preparation<br>Multi-strain probiotic mixture. The daily dose was five billion (2 capsules/day). | Dietary Supplement: Multi-strain probiotic mixture of four Bifidobacterium, five Lactobacillus and one Streptococcus species or placebo<br>* Oral supplementation with multi-strain probiotic preparation<br>|
| Placebo Comparator: Maltodextrin<br>Maltodextrin comparable in color, texture and taste to the probiotic mixture (2 capsules/day). | Dietary Supplement: Maltodextrin<br>* Maltodextrin as placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in severity of IBS symptoms using IBS Severity Scoring System (IBS-SSS) | IBS-Severity Scoring System is a 5-question survey that asks: 1. the severity of abdominal pain, 2. frequency of abdominal pain, 3. severity of abdominal distention, 4.dissatisfaction with bowel habit, and 5. interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Each of the five question generates a maximum score of 100 point, and total scores can range from 0-500 with higher scores indicating severe symptoms. A decrease of 30 points is associated with a clinically meaningful improvement. | From baseline at 4 and 8 weeks of intervention | 
| Improvement or worsening of IBS global symptoms using Global Improvement Scale (IBS-GIS) | IBS-Global Improvement Scale asseses IBS symptoms using a patient-defined 7 point Linkert scale ranging from symptoms substantially worse to substantially improved. Patients answer the question Have you felt any change in the severity of your symptoms over the past 7 days compared to how you felt before the medicine was given? The answers are recorded based on the 7-point scale: I feel that the symptoms have worsened significantly I feel that the symptoms have moderately worsened I feel that the symptoms have slightly worsened I feel no change I feel a slight improvement I feel moderate improvement I feel significant improvement IBS-GIS score indicates: improvement if is >4 or worsening if is<4, no change if is 4 | From baseline at 4 and 8 weeks of intervention | 
| Changes in adequate relief of IBS symptoms (IBS-AR) | IBS-Adequate Relief (IBS-AR) is a dichotomous single item that asks participants Over the past week (7 days) have you had adequate relief of your IBS symptoms? The answer is YES or NO. | From baseline at 4 and 8 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in type of stools | ype of stool assessed before intervention and then 3 times a week. Type of stools assessed using the Bristol Stool Scale. Bristol Scale is designed to classify faeces into seven groups: type 1-2 indicate constipation, type 3-4 are normal stools; type 5-7 indicate diarrhea. | From baseline for 8 weeks of intervention | 
| Changes in number of bowel movements per day | Number of bowel movements per day assessed before intervention and then 3 times a week | From baseline for 8 weeks of intervention | 
| Changes in severity of pain | The severity of pain assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no pain, and 1-4 the severity of pain with higher scores indicating worse pain | From baseline for 8 weeks of intervention | 
| Changes in flatulence | The severity of flatulence assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no flatulence, and points1-4 with higher scores indicating worse flatulence | From baseline for 8 weeks of intervention | 
| Changes in feeling of incomplete evacuation of stool | The severity of incomplete evacuation of stool assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no feeling of incomplete evacuation of stool, and points1-4 with higher scores indicating worse feeling of incomplete evacuation of stool | From baseline for 8 weeks of intervention | 
| Changes in the occurrence of adverse events | The number and the type of adverse events assessed before intervention and then 3 times a weeks. | From baseline for 8 weeks of intervention |