Antibiotic Treatment Trial for Small Intestinal Bacterial Overgrowth

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

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).

Study Overview

• Status: Unknown
• Conditions: Small Intestinal Bacterial Overgrowth
• Intervention / Treatment: Drug: Placebo; Drug: Ciprofloxacin; Drug: Metronidazole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Placebo given twice daily for 14 days; Other Names: sugar pill
Active Comparator: Ciprofloxacin; 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; Ciprofloxacin 500mg given twice daily for 14 days; Other Names: fluoroquinolone; cipro
Active Comparator: Metronidazole; 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; Metronidazole 500mg given twice daily for 14 days; Other Names: flagyl; metro

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: San Antonio Military Medical Center
• Investigators: Principal Investigator: Karin S Gilkison, MD, MPH, Gastroenterology Fellow

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: April 10, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Estimate): June 1, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Metronidazole; Ciprofloxacin; Fluoroquinolones
• Other Study ID Numbers: 398092-1