Antibiotic Treatment Trial for Small Intestinal Bacterial Overgrowth

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy of ciprofloxacin versus metronidazole versus placebo in eradication of small intestinal bacterial overgrowth (SIBO).

Detailed Description
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Approximately 180 study subjects with SIBO identified by positive glucose hydrogen breath (GHB) testing who meet inclusive and exclusive criteria will be randomized to receive either ciprofloxacin 500mg by mouth twice daily, metronidazole 500mg by mouth twice daily, or placebo by mouth twice daily. Subjects will complete a baseline symptom questionnaire and be treated for 14 days. Response will be assessed at end of treatment. The Gastrointestinal Symptom Rating Scale (GSRS) and GHB testing will be performed at the end of treatment. Subjects with a negative GHB at the end of treatment are considered as cured, or treatment success. Patients with treatment success will be reassessed for long-term response to treatment or disease recurrence at 30 days, 4 months, and 9 months using GHB. Symptoms will also be re-assessed at the 30 day, 4 month, and 9 month intervals with GSRS-IBS symptom questionnaire done prior to GHB testing.

Official Title
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Antibiotic Treatment Trial for Small Intestinal Bacterial Overgrowth: A Randomized, Double-Blind, Placebo-Controlled Trial Comparing Ciprofloxacin and Metronidazole

Conditions
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Small Intestinal Bacterial Overgrowth

Intervention / Treatment
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* Drug: Metronidazole
* Drug: Ciprofloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients age greater than 18 who have been diagnosed with SIBO after a clinically indicated hydrogen breath test. Patients with liver disease or liver cirrhosis will be included, as this particular group is at higher risk for developing SIBO, would potentially benefit from inclusion, and do not require dose adjustments with either study medication. Patients on warfarin are not excluded, but INR will be uniformly recommended to be checked within 1 week of therapy initiation, as standard practice through the Coumadin clinic, for the potential effect on INR and increased risk of bleeding while on any antibiotic Exclusion Criteria: Patient age less than 18 Hypersensitivity to the antibiotics Pregnancy or breast feeding Patients who cannot consent for themselves End stage renal disease defined as creatinine clearance <30 mL/min or on hemodialysis. Patients who have taken antibiotics in the past 30 days Laxatives, stool softeners, or bulk fiber in the last 7 days Enemas or suppositories in the last 3 daysⱡ

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsule: To be provided by BAMC Pharmacy. It will be made and stored by BAMC pharmacy. The matching placebo will be a gelatin capsule filled with methylcellulose powder only. Patient will take 2 capsules two times a day for 14 days. | Drug: Placebo<br>* Placebo given twice daily for 14 days<br>* Other names: sugar pill;|
| Active Comparator: Ciprofloxacin<br>Ciprofloxacin 250mg capsule: To be provided by BAMC pharmacy. It will be made and stored by BAMC Pharmacy. Ciprofloxacin 250mg tablet will be encapsulated with a gelatin capsule filled with methylcellulose. Patient will take 2 capsules of Ciprofloxacin 250mg two times a day for 14 days. | Drug: Ciprofloxacin<br>* Ciprofloxacin 500mg given twice daily for 14 days<br>* Other names: fluoroquinolone;|
| Active Comparator: Metronidazole<br>Metronidazole 250mg capsule: To be provided by BAMC pharmacy. It will be made and stored by BAMC Pharmacy. Metronidazole 250mg will be encapsulated with a gelatin capsule filled with methylcellulose. Patient will take 2 capsules of metronidazole 250mg two times a day for 14 days. | Drug: Metronidazole<br>* Metronidazole 500mg given twice daily for 14 days<br>* Other names: metro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients cured of SIBO after treatment with ciprofloxacin versus metronidazole versus placebo. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal symptoms based on questionnaire |  | Immediately post-treatment (approximately 2 weeks), 30 days, 4 months, and 9 months | 
| Disease relapse rate of SIBO after treatment success |  | Immediately post-treatment (approximately 2 weeks), 30 days, 4 months, and 9 months | 
| Time interval between treatment success and recurrence of SIBO |  | Immediately post-treatment (approximately 2 weeks), 30 days, 4 months, and 9 months |