Clinical trial NCT00786123: Exploring the Mechanism of a Probiotic Combination VSL#3 in Irritable Bowel Syndrome
Official title: Exploring the Mechanism of a Probiotic Combination VSL#3 in Irritable Bowel Syndrome: a Randomized Double Blind Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: irritable bowel syndrome
rectal hypersensitivity
probiotics
melatonin
brain-gut axis
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2008-11-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Irritable bowel syndrome (IBS) is a very common chronic gastrointestinal disorder. Existing therapies for IBS are still far from satisfactory and new therapies are being constantly sought. Probiotics are promising candidate for the prevention and treatment of IBS. However, its efficacy and mechanism is still unclear. The current study aims to evaluate the effects of a combination probiotic, VSL#3, on symptoms and rectal sensitivity in patients with IBS. The underlying mechanism will also be investigated. We will recruit forty patients with Rome III IBS and randomized them, in a parallel group, double-blinded design, to take four VSL#3 capsules or placebos, twice daily, for six weeks. Before and after treatment, patients will be assessed for their symptoms, rectal sensitivity, as well as saliva and fecal melatonin levels. Bowel symptom diary and weekly satisfactory relief of bowel symptoms will also be recorded and evaluated.


Eligibility criteria: Inclusion Criteria:

* Female and male patients with IBS between the ages of 18 and 68 will be recruited. IBS will be diagnosed according to the Rome III diagnostic criteria (Drossman and Dumitrascu, 2006). The history of previous chronic GI symptoms suggestive of IBS should be at least 3 months (not necessarily consecutive) over the preceding 6 months. The stool culture of each subject should be negative for hemoccult, pathogens (Salmonella and Shigella), parasites (Giardia) and ova/ cyst. Only patients who had IBS symptoms for at least one month prior to the study and whose IBS symptom score is of at least a moderate severity on at least one of IBS symptoms will be eligible for inclusion into the study.

Exclusion Criteria:

* Those subjects who are unwilling or unable to give informed consent, follow protocol or to stop all medications used to treat diarrhoea or colitis
* Subject taking at the time of proposed enrolment any of the below listed prohibited medications:

  * Anticholinergics (dicyclomine, hyoscyamine, propantheline)
  * Cholinomimetic agents (bethanechol etc.)
  * All narcotics (morphine, codeine, propoxyphene either alone or in any
  * combination)
  * 5-HT3 receptor antagonists (e.g., alosetron, ondansetron, tropisetron, dolasetron, granisetron).
  * Gastrointestinal preparations:
  * Antacids (containing either magnesium or aluminium)
  * Antidiarrheal agents
  * Bismuth compounds
  * Laxatives (stimulant or osmotic)
  * Sulfasalazine
* Treatment with immunosuppressive medications or presence of an immunocompromised state
* If currently using medication (like those used in Diabetes mellitus, Sarcoidosis, Connective tissue disease, poorly controlled hypo/hyperthyroidism) may alter bowel motility or if under long term antibiotic therapy
* Use of any other investigational drug and/or participation in any clinical trial within 3 months of entry to this study
* Patients will be excluded if they had undergone previous abdominal surgery (except appendectomy, Caesarean section, Cholecystectomy, Tubal ligation, Hysterectomy, Hernia repair ≥ 6 months prior to enrolment)
* Subject who has been diagnosed with any of the following GI disorders:

  * Inflammatory bowel disease (Crohn's disease, Ulcerative colitis, Indeterminate Colitis
  * Microscopic colitis (lymphocytic colitis, collagenous colitis)
  * Celiac Disease
  * Gastroparesis
  * Gastrointestinal obstruction and/or stricture
  * Chronic pancreatitis
* Subject with a significant concomitant psychiatric, neurological, metabolic, renal, hepatic, infections, hematological, C.V or pulmonary illness, unless condition is stable and judged by the investigator that such condition does not interfere with the patients participation in the study.

Primary outcomes:
measure: Resolution of symptoms
timeFrame: 6 weeks
Secondary outcomes:
measure: Rectal sensitivity
timeFrame: 6 weeks
measure: Saliva and fecal melatonin levels
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Ho Khek Yu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Camilleri M. Is there a role for probiotics in irritable bowel syndrome? Dig Liver Dis. 2006 Dec;38 Suppl 2:S266-9. doi: 10.1016/S1590-8658(07)60007-3.
citation: Shen B, Brzezinski A, Fazio VW, Remzi FH, Achkar JP, Bennett AE, Sherman K, Lashner BA. Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice. Aliment Pharmacol Ther. 2005 Oct 15;22(8):721-8. doi: 10.1111/j.1365-2036.2005.02642.x.
citation: Song GH, Venkatraman V, Ho KY, Chee MW, Yeoh KG, Wilder-Smith CH. Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. Pain. 2006 Dec 15;126(1-3):79-90. doi: 10.1016/j.pain.2006.06.017. Epub 2006 Jul 18.
citation: Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005 Oct;54(10):1402-7. doi: 10.1136/gut.2004.062034. Epub 2005 May 24.