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The Irritable Bowel Syndrome (IBS) is a frequent disease, affecting between 10 and 20% of general population. Several pathophysiologic mechanisms have been described in IBS, among them the role of intestinal microbiota and small intestinal bacterial overgrowth (SIBO) have received special attention. SIBO has an adequate response to antibiotic treatment, unfortunately it didn't have an adequate diagnostic test: The classic gold standard -jejunal aspirate culture- has been criticized due to lack of standardization; the breath tests are simpler and widely available, but they have also been criticized due to inadequate diagnostic accuracy for SIBO. For this reason seems important to evaluate the performance of breath tests in terms of predicting clinical benefit of antibiotic therapy in IBS patients, rather than predicting a positive culture and SIBO.
The objectives of this study are:
After signing the informed consent, all patients will be submitted to both glucose and lactulose breath tests within a 10 days period. The order of the test will be randomized using a random number list of allocation, which will not be known by the patient. For the lactulose test a 10 g and for the glucose test a 50 g dose will be used, as previously suggested.
After the second test, patients will receive Rifaximin 400 mg TID (1200 mg/day) for 10 days. In the case of methane producers (defined as patients with basal methane levels > 3 ppm) Neomycin 500 mg BID (1000 mg/day) for ten days will be added, as suggested by Low et al.
Two weeks after the antibiotic course, patients will be cited and the following data will be assessed: 1. Adequate relief for global IBS symptoms. 2. Adequate relief for bloating. 3. Evaluation of IBS severity using IBSSS. 4. Drug induced side effects. Only after that information is submitted by the patient, the results of the test will be revealed.
Patients will be classified as responders or not according to their global symptoms adequate relief status. Using this as gold standard criterion, the test performance, in terms of sensitivity, specificity, positive and negative predictive value, will be calculated for the following tests:
The different tests will be compared in terms of their performance at the optimal cutoff value and calculating the area under the ROC curve.
The sample size was calculated as previously suggested. Using Shah et al data, we assumed a sensitivity of 72% and a specificity of 66% for the lactulose breath test. Using an alpha and beta error of 5% and 20%, respectively, and a disease prevalence of 35% (SIBO in IBS), we estimate a sample size of 120 patients.
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| Measure | Description | Time Frame |
|---|---|---|
| Adequate relief for global IBS symptoms | Adequate relief corresponds to the answer of the patient (yes or no) to the question ´have you achieved adequate relief from your symptoms?¨ | Two weeks after the antibiotic course |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of IBS severity using IBSSS | IBSSS is a score (mainly visual analogue scale (VAS) based) consisting of several questions regarding different IBS symptoms. The binary outcome adequate relief and a severity evaluation by IBSSS are the recommended outcomes by the designing of clinical trials Rome committee. All patients will be characterized in terms of basal IBS severity using IBSSS (before to course of 10 days of antibiotics). |
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Inclusion Criteria:
Exclusion Criteria:
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Patients meeting Rome III criteria for IBS.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniel Cisternas, MD | Contact | 56-2-3543820 | dcisterc@gmail.com | |
| Roberto Candia, MD | Contact | 56-2-3543820 | roberto.candia@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Daniel Cisternas, MD | Pontificia Universidad Catolica de Chile | Study Director |
| Roberto Candia, MD | Pontificia Universidad Catolica de Chile | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Gastroenterology, Pontificia Universidad Catolica de Chile | Santiago | Metropolitan | 8330024 | Chile |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18513268 | Background | Parkes GC, Brostoff J, Whelan K, Sanderson JD. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment. Am J Gastroenterol. 2008 Jun;103(6):1557-67. doi: 10.1111/j.1572-0241.2008.01869.x. Epub 2008 May 29. | |
| 15316000 | Background | Lin HC. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852-8. doi: 10.1001/jama.292.7.852. |
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| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
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| Two weeks after antibiotic course |
| Adequate relief for bloating. | Adequate relief of bloating corresponds to the answer of the patient (yes or no) to the question ´have you achieved adequate relief from your bloating?¨. | Two weeks after the antibiotic course |
| Drug induced side effects. | Two weeks after antibiotic course |
| Patricio Ibañez, MD |
| Pontificia Universidad Catolica de Chile |
| Principal Investigator |
| Juan Pablo Ortega, MD | Pontificia Universidad Catolica de Chile | Principal Investigator |
| 21844910 | Background | DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011 Aug 16;8(9):523-31. doi: 10.1038/nrgastro.2011.133. |
| 19344474 | Background | Gasbarrini A, Corazza GR, Gasbarrini G, Montalto M, Di Stefano M, Basilisco G, Parodi A, Usai-Satta P, Vernia P, Anania C, Astegiano M, Barbara G, Benini L, Bonazzi P, Capurso G, Certo M, Colecchia A, Cuoco L, Di Sario A, Festi D, Lauritano C, Miceli E, Nardone G, Perri F, Portincasa P, Risicato R, Sorge M, Tursi A; 1st Rome H2-Breath Testing Consensus Conference Working Group. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther. 2009 Mar 30;29 Suppl 1:1-49. doi: 10.1111/j.1365-2036.2009.03951.x. |
| 16678567 | Background | Design of Treatment Trials Committee; Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJ. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2006 Apr;130(5):1538-51. doi: 10.1053/j.gastro.2005.11.058. |
| Background | Fleiss, J.L., Statistical methods for rates and proportions. 2d ed. Wiley series in probability and mathematical statistics. 1981, New York: Wiley. xviii, 321 p |
| 16018921 | Background | Flahault A, Cadilhac M, Thomas G. Sample size calculation should be performed for design accuracy in diagnostic test studies. J Clin Epidemiol. 2005 Aug;58(8):859-62. doi: 10.1016/j.jclinepi.2004.12.009. |
| 12190153 | Result | Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002 Aug;97(8):1910-5. doi: 10.1111/j.1572-0241.2002.05913.x. |
| 15916618 | Result | Gwee KA. Irritable bowel syndrome in developing countries--a disorder of civilization or colonization? Neurogastroenterol Motil. 2005 Jun;17(3):317-24. doi: 10.1111/j.1365-2982.2005.00627.x. |
| 17520365 | Result | Yang J, Lee HR, Low K, Chatterjee S, Pimentel M. Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. 2008 Jan;53(1):169-74. doi: 10.1007/s10620-007-9839-8. Epub 2007 May 23. |
| 10792117 | Result | Di Stefano M, Malservisi S, Veneto G, Ferrieri A, Corazza GR. Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2000 May;14(5):551-6. doi: 10.1046/j.1365-2036.2000.00751.x. |
| 19499846 | Result | Lauritano EC, Gabrielli M, Scarpellini E, Ojetti V, Roccarina D, Villita A, Fiore E, Flore R, Santoliquido A, Tondi P, Gasbarrini G, Ghirlanda G, Gasbarrini A. Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):111-6. |
| 17990113 | Result | Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008 Jun;53(6):1443-54. doi: 10.1007/s10620-007-0065-1. |
| 9146781 | Result | Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x. |
| 20467896 | Result | Shah ED, Basseri RJ, Chong K, Pimentel M. Abnormal breath testing in IBS: a meta-analysis. Dig Dis Sci. 2010 Sep;55(9):2441-9. doi: 10.1007/s10620-010-1276-4. Epub 2010 May 14. |
| D004066 | Digestive System Diseases |