Lactulose and Glucose Breath Tests as Predictors of Clinical Benefit From Rifaximin in Irritable Bowel Syndrome

NCT ID: NCT01803724

Last Updated: 2013-03-04

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2014-12-31

Brief Summary

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:

1. Determine which breath test (lactulose or glucose) predicts better a potential clinical benefit of antibiotic treatment (Rifaximin) in IBS patients.

2. Determine which of the multiples diagnostic criteria described for the lactulose breath test predicts better a potential clinical benefit Rifaximin in IBS patients.

Detailed Description

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:

1. Glucose breath test. A ROC curve will be calculated to determine the best cutoff value

2. Lactulose breath test using the rise occurring before 60 min, without the presence of a double peak. A ROC curve will be calculated to determine the best cutoff value

3. Lactulose breath test using the rise occurring before 60 min, if there is a double peak. A ROC curve will be calculated to determine the best cutoff value

4. Lactulose breath test using the rise occurring before 90 min, without the presence of a double peak. A ROC curve will be calculated to determine the best cutoff value

5. Lactulose breath test using the rise occurring before 90 min, if there is a double peak. A ROC curve will be calculated to determine the best cutoff value

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.

Conditions

Irritable Bowel Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients meeting Rome III criteria for IBS.

Exclusion Criteria

1. Patients < 18 years old

2. Previous intestinal (small or large bowel) resection

3. Known anatomical intestinal alterations, including diverticula and stenosis

4. Inflamatory bowel disease (Crohn´s or ulcerative colitis)

5. Presence of IBS alarm signs suggestive of organic disease, including anemia or family history of celiac disease or colon cancer

6. Recent acute onset diarrhea

7. Pregnancy

8. Neurologic or psychiatric disease that may not allow the patient to appropriately describe clinical outcomes

9. Presence of a disease that could affect intestinal transit, such as Parkinson´s, Chronic Intestinal Pseudobstruction, Scleroderma, Diabetes mellitus, etc

10. Impossibility to transitory withdraw drugs that affect intestinal transit, such as Calcium channel blockers, tricyclics

11. Inability to sign or rejection to informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Cisternas, MD

Role: STUDY_DIRECTOR

Pontificia Universidad Catolica de Chile

Roberto Candia, MD

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Patricio Ibañez, MD

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Juan Pablo Ortega, MD

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Locations

Department of Gastroenterology, Pontificia Universidad Catolica de Chile

Santiago, Metropolitan, Chile

Countries

Chile

Central Contacts

Daniel Cisternas, MD

Role: CONTACT

dcisterc@gmail.com

56-2-3543820

Roberto Candia, MD

Role: CONTACT

roberto.candia@gmail.com

56-2-3543820

Facility Contacts

Daniel Cisternas, MD

Role: primary

dcisterc@gmail.com

56-2-3543820

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Other Identifiers

PUC-0003

Identifier Type: -

Identifier Source: org_study_id