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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by Pontificia Universidad Catolica de Chile
Sponsor:
Information provided by (Responsible Party):
Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier:
NCT01803724
First received: March 1, 2013
Last updated: NA
Last verified: March 2013
History: No changes posted
  Purpose

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.

Condition
Irritable Bowel Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Comparison Between Lactulose and Glucose Breath Tests as Predictors of Clinical Benefit From Rifaximin in Irritable Bowel Syndrome Patients

Resource links provided by NLM:


Further study details as provided by Pontificia Universidad Catolica de Chile:

Primary Outcome Measures:
  • Adequate relief for global IBS symptoms [ Time Frame: Two weeks after the antibiotic course ] [ Designated as safety issue: No ]
    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:
  • Evaluation of IBS severity using IBSSS [ Time Frame: Two weeks after antibiotic course ] [ Designated as safety issue: No ]

    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. [ Time Frame: Two weeks after the antibiotic course ] [ Designated as safety issue: No ]
    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. [ Time Frame: Two weeks after antibiotic course ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: May 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients meeting Rome III criteria for IBS.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803724

Contacts
Contact: Daniel Cisternas, MD 56-2-3543820 dcisterc@gmail.com
Contact: Roberto Candia, MD 56-2-3543820 roberto.candia@gmail.com

Locations
Chile
Department of Gastroenterology, Pontificia Universidad Catolica de Chile Not yet recruiting
Santiago, Metropolitan, Chile, 8330024
Contact: Daniel Cisternas, MD    56-2-3543820    dcisterc@gmail.com   
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
Study Director: Daniel Cisternas, MD Pontificia Universidad Catolica de Chile
Principal Investigator: Roberto Candia, MD Pontificia Universidad Catolica de Chile
Principal Investigator: Patricio Ibañez, MD Pontificia Universidad Catolica de Chile
Principal Investigator: Juan Pablo Ortega, MD Pontificia Universidad Catolica de Chile
  More Information

Publications:

Responsible Party: Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier: NCT01803724     History of Changes
Other Study ID Numbers: PUC-0003
Study First Received: March 1, 2013
Last Updated: March 1, 2013
Health Authority: Chile: Institutional Review Board

Keywords provided by Pontificia Universidad Catolica de Chile:
Irritable Bowel Syndrome
Small Intestinal Bacterial Overgrowth
Lactulose breath test
Glucose breath test
Rifaximin

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Rifaximin
Lactulose
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 23, 2014