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

• Conditions: Irritable Bowel Syndrome

• Registration Number: NCT01803724
• Lead Sponsor: Pontificia Universidad Catolica de Chile

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.

Study Timeline

• Status Verified: 2013-03
• Study First Submitted: 2013-03-01
• Study First Submitted QC: 2013-03-01
• Last Update Submitted: 2013-03-01
• Study First Posted: 2013-03-04
• Last Update Posted: 2013-03-04
• Study Start: 2013-05
• Primary Completion: 2014-06
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adequate relief for global IBS symptoms	Two weeks after the antibiotic course	Adequate relief corresponds to the answer of the patient (yes or no) to the question ´have you achieved adequate relief from your symptoms?¨

Secondary Outcome Measures

Name	Time	Method
Evaluation of IBS severity using IBSSS	Two weeks after antibiotic course	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).
Adequate relief for bloating.	Two weeks after the antibiotic course	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?¨.
Drug induced side effects.	Two weeks after antibiotic course

Trial Locations

Locations (1)

Department of Gastroenterology, Pontificia Universidad Catolica de Chile; 🇨🇱 Santiago, Metropolitan, Chile