Clinical trial NCT01667627: Probiotic in Irritable Bowel Syndrome (IBS) Patients With Diarrhea
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: IBS
Keywords: IBS
Probiotic
hs-CRP
Cholinergic status
Micro-inflammation
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2012-08-17
Enrollment: 107
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

A diagnosis of IBS-D according to the Rome III criteria, agreement to participate and the ability to sign an informed consent. Moreover, the definition of inclusion criteria is based on the FDA Draft Guidance for Clinical Evaluation of Products (add ref here). Over the two week run-in period:

* Pain Intensity: weekly average of worst abdominal pain in past 24 hours score of ≥ 3.0 on a 0 (no pain at all) to 10 (worst possible pain) point scale
* Stool Consistency: ≥30% of days/week with at least one stool ≥6 using the Bristol Stool Score (BSS, Fig. 1) (ref).

Exclusion Criteria:

1) Hyperthyroidism, 2) celiac disease 3) pregnancy, 4) other gastrointestinal diagnoses that might interfere with the study (e.g. active peptic disease, inflammatory bowel disease), 5) a history of malignancy that might, to the best judgment of the doctor, interfere with the study, 6) any infectious or inflammatory disease within the last month, 7) active medically treated asthma, 8) baseline levels of HsCRP \> 10mg/liter, 9) steroid treatment for any indication, 10) fecal incontinence, and 11) treatment with probiotics or antibiotics of any kind within the last 4 weeks, 11) Diabetes.

Primary outcomes:
measure: Symptom relief (abdominal pain and stool consistency)
timeFrame: 8 weeks
Secondary outcomes:
measure: Improvement in other specific IBS symptoms, i.e., gas and bloating, feeling of urgency
timeFrame: 8 weeks
measure: Reduce hs-CRP levels
timeFrame: 8 weeks
measure: Improve the cholinergic status
timeFrame: 8 weeks
measure: Reduce calprotectin levels
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
state: Central Israel
Study officials:
affiliation: Tel Aviv Medical Center
name: Ami Sperber, MD
role: STUDY_DIRECTOR
affiliation: Tel Aviv Medical Center
name: Roy Dekel, MD
role: PRINCIPAL_INVESTIGATOR
References: