- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04414722
Mechanisms of Probiotics and Antibiotic-Associated Diarrhea (OURBIOTIC)
Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, the efficacy of many probiotic products used for AAD is not supported by rigorous independent research, and non-evidence-based clinical usage is common. Data from several studies are consistent with the notion that antibiotic-induced disruption of commensal bacteria in the colon results in a significant reduction of short chain fatty acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting in AAD. The probiotic strain being studied, Bifidobacterium animalis subsp. lactis BB-12 (BB-12), has been shown to ameliorate a variety of gastrointestinal disease states and is known to produce acetate at concentrations up to 50 mM in vitro. Thus, the investigators hypothesize that administration of BB-12 at the same time as antibiotic consumption will protect against the development of AAD through its ability to generate acetate directly, and also increase other SCFAs through cross-feeding of certain bacteria in the Firmicutes phylum such Clostridium, Eubacterium and Roseburia, which use acetate to produce butyrate.
The primary aim is to determine the ability of BB-12 to impact antibiotic-induced reduction in SCFA as reflected by the levels of acetate, the most abundant primary colonic SCFA, and assess temporal intervals of probiotic administration. The primary hypothesis is that antibiotics will result in a reduction in fecal SCFA, but BB-12 supplementation will protect against antibiotic-induced SCFA reduction and/or be associated with a more rapid return to baseline SCFA levels as compared to controls. Antibiotics also result in a decrease in total microbial counts and diversity in the gut microbiota, disrupting the homeostasis of the gut ecosystem and allowing colonization by pathogens. We hypothesize that concurrent administration of the probiotic and antibiotic is not necessary for the probiotic impact on SCFA.
The secondary aim will be to determine the ability of BB-12 to impact antibiotic-induced disruption of the gut microbiota with 16S ribosomal ribonucleic acid (rRNA) profiling, and assess temporal intervals of probiotic administration. The secondary hypothesis is that antibiotics will result in a decrease in the overall number and diversity of bacterial species present in the fecal microbiota, and further BB-12 supplementation will protect against antibiotic-induced shifts in the microbiota and/or will be associated with a more rapid return to a baseline microbiota composition as compared to controls. We hypothesize that concurrent administration of the probiotic and antibiotic is not necessary for the probiotic effect on the composition of the gut microbiota.
The tertiary aim is to longitudinally characterize the gut microbiota with high-throughput metatranscriptomics in order to generate complementary information on the impact of antibiotics plus and minus BB-12 on overall microbiome function. We hypothesize that acetate produced by BB-12 in situ will cross-feed butyrate producers in the Firmicutes phylum resulting in an up-regulation of butyrate biosynthetic pathways.
The long-term goal is to determine the impact of BB-12 on a variety of gastrointestinal disease states and ages, through high-level independent research. This mechanism elucidation is important for directing future translational and effectiveness research.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Daniel Merenstein, MD
- Phone Number: 202-687-2745
- Email: djm23@georgetown.edu
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
- Georgetown University Department of Family Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Has the ability to read, speak, and write in English
- Has a refrigerator (for proper storage of the study yogurt)
- Has reliable telephone access
- Is between ages of 18-65 years
- Agree to refrain from eating yogurts, yogurt drinks, and other foods specified in the provided list
- Agree to collect stool samples and participate in follow-up calls as specified
Exclusion Criteria:
- Diabetes or asthma that requires medication
- Allergy to strawberry
- Active diarrhea (three or more loose stools per day for two consecutive days)
- Any gastrointestinal (or digestive tract) medications, i.e. medicines for irritable bowel syndrome, gastroesophageal (acid) reflux disease, inflammatory bowel disease, etc.
- History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic
- History of gastrointestinal surgery or disease
- Lactose intolerance that prevents participant from eating yogurt
- Allergy to milk-protein
- Allergy to any component of the product or the yogurt vehicle
- Allergy to penicillin or cephalosporin class antibiotics
- Allergy to any of the following medications: a) Penicillin; b) Erythromycin; c) Tetracycline; d) Trimethoprim; e) Ciprofloxacin
- Women who are breastfeeding, pregnant, or planning to become pregnant during the study
- Was a participant in the "YOBIOTIC" study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Concurrent control yogurt and amoxicillin-clavulanate
Yogurt without Bifidobacterium animalis subsp.
lactis BB-12 (BB-12) and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time
|
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Other Names:
Yogurt without Bifidobacterium animalis subsp.
lactis BB-12 (BB-12)
|
Placebo Comparator: Control yogurt taken 4 hours after amoxicillin-clavulanate
Yogurt without Bifidobacterium animalis subsp.
lactis BB-12 (BB-12) taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet
|
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Other Names:
Yogurt without Bifidobacterium animalis subsp.
lactis BB-12 (BB-12)
|
Active Comparator: Concurrent BB-12 yogurt and amoxicillin-clavulanate
Bifidobacterium animalis subsp.
lactis BB-12-supplemented yogurt and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time
|
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Other Names:
Bifidobacterium animalis subsp.
lactis BB-12 (BB-12)-supplemented yogurt
Other Names:
|
Active Comparator: BB-12 yogurt taken 4 hours after amoxicillin-clavulanate
Bifidobacterium animalis subsp.
lactis BB-12-supplemented yogurt taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet
|
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Other Names:
Bifidobacterium animalis subsp.
lactis BB-12 (BB-12)-supplemented yogurt
Other Names:
|
Other: Amoxicillin-clavulanate
Amoxicillin-clavulanate 875 mg-125 mg oral tablet
|
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
Time Frame: day 7
|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
|
day 7
|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
Time Frame: day 30
|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
|
day 30
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in baseline diversity of bacterial species in fecal microbiota
Time Frame: day 7, 14
|
Change in baseline diversity of bacterial species in fecal microbiota
|
day 7, 14
|
Change in baseline number of bacterial species in fecal microbiota
Time Frame: day 7, 14
|
Change in baseline number of bacterial species in fecal microbiota
|
day 7, 14
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
Time Frame: day 14, 21
|
Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)
|
day 14, 21
|
Change in reported symptoms: diarrhea/stool frequency, loose stool, constipation, fever, flatulence, lack of appetite, pain, rash, vomiting, allergic reaction, dyspepsia, and nausea.
Time Frame: day 7, 14, 21, 30
|
Change in reported symptoms: diarrhea/stool frequency, loose stool, constipation, fever, flatulence, lack of appetite, pain, rash, vomiting, allergic reaction, dyspepsia, and nausea.
|
day 7, 14, 21, 30
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Daniel Merenstein, MD, Georgetown University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2020-2431
- R33AT009622 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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