Probiotic in Irritable Bowel Syndrome (IBS) Patients With Diarrhea (IBS-D)
We present the study design of a clinical trial designed to assess the clinical effects of the multispecies probiotic combination "BIO-25" in IBS-D patients. To this aim the primary endpoints of the study will be improvement in abdominal pain and stool consistency. The study will also be designed and powered to investigate the effect of the probiotic BIO-25 on the putative inflammation-associated parameters related to microinflammation in IBS, using postulated improvements in Hs-CRP, and calprotectin as markers of that effect. Additional aims of the study will examine the possible effect of probiotic BIO-25 on the cholinergic status.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-blind, Placebo-controlled Study to Assess the Effect of Probiotic on Symptom Relief and Indices of Micro-inflammation and Cholinergic Status in IBS Patients With Diarrhea.|
- Symptom relief (abdominal pain and stool consistency) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Abdominal pain intensity, stool consistency, will be assessed by visual analogue scales (VAS) with scales from 0 (no symptom at all) to 10 (the worst possible symptom.
The definition of treatment responders is based on the FDA Draft Guidance for Clinical Evaluation of Products for Treatment of Irritable Bowel Syndrome.
- A Pain Intensity Responder is a patient who experiences a 30% or greater decrease in the weekly average of worst abdominal pain in past 24 hours in the past 24 hours compared to baseline.
- A Stool Consistency Responder is a patient who has a greater than 50% decrease in the number of days with at least one stool ≥ type 6 using the Bristol Stool Scale (BSS).
- A patient will be classified as an overall responder if they achieve the above improvement in pain intensity and stool consistency for at least 50 percent of the time.
- Improvement in other specific IBS symptoms, i.e., gas and bloating, feeling of urgency [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Specific IBS symptoms, i.e., gas and bloating, feeling of urgency, will be assessed by visual analogue scales (VAS) with scales from 0 (no symptom at all) to 10 (the worst possible symptom).
- Reduce hs-CRP levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Blood will be drawn from IBS-D patients after a 12-hour fast and will be analyzed for hs-CRP.
- Improve the cholinergic status [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Plasma cholinesterase catalytic activity measurements will involve adaptation of a spectrophotometric method to a microtiter plate assay
- Reduce calprotectin levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
At the beginning and at the end of the treatment period, fecal samples will be obtained for the measurement of calprotectin levels.
The quantitative concentration of calprotectin will be determined by enzyme linked immunosorbent assay (ELISA).
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Active Comparator: BIO-25, Probiotic-mixture
Two capsules a day.
Dietary Supplement: Bio-25
Each capsule of the multispecies probiotic combination Bio-25 consists of 25 billion live bacteria.
Each type of bio-25 contains billions of live lactic acid bacteria in defined ratios of lyophilized Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasein, Lactobacillus casei, Bifidobacterium bifidum,Lactobacillus lactis, Lactobacillus rhamnosus,and Streptococcus thermophilus.
Other Name: Probiotic
Placebo Comparator: Placebo
Identical to the Bio-25 capsule: same taste, same colour, same appearance
Probiotic treatment in IBS is safe and effective. Probiotics have been shown to improve the anti-inflammatory/proinflammatory ratio, and may also improve intestinal motility, and the bacterial composition of the intestines. There is a substantial body of evidence in support of the use of probiotics in IBS. Probiotics appear to be particularly effective in the reduction of abdominal bloating and discomfort. The strains of the multispecies probiotic combination (BIO-25 LR) were tested and found to be beneficial in well-designed studies of IBS patients. Patients with post-infectious IBS, as well as many patients with "classic" IBS, manifest a low-grade inflammatory state that may be associated with visceral hypersensitivity and impaired motility. Probiotics may suppress this low-grade inflammation. In a recent study we found that highly sensitive CRP (hs-CRP), a serum marker of micro-inflammation, was significantly higher in patients with diarrhea-predominant IBS than healthy controls, although within normal limits in both groups. Thus, hs-CRP may serve as a marker of this low-grade, sub-clinical inflammation. If treatment with probiotic reduces the degree of low-grade inflammation in IBS, the improvement may be reflected in reduced hs-CRP levels. This study can contribute to our understanding of the pathophysiology of IBS and provide further evidence for the effectiveness of probiotic in its treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01667627
|Contact: Keren Hod, MsCfirstname.lastname@example.org|
|Tel-Aviv Sourasky Medical Center||Not yet recruiting|
|Tel-Aviv, Central Israel, Israel|
|Principal Investigator: Roy Dekel, MD|
|Study Director:||Ami Sperber, MD||Tel Aviv Medical Center|
|Principal Investigator:||Roy Dekel, MD||Tel Aviv Medical Center|