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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03755765
Other study ID # 2018-0736
Secondary ID 1R61AT009622-01A
Status Completed
Phase Early Phase 1
First received
Last updated
Start date July 23, 2019
Est. completion date January 8, 2020

Study information

Verified date February 2023
Source Georgetown University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The focus of the study is to better understand the mechanisms causing antibiotic-associated diarrhea (AAD) and how probiotics may prevent some of the iatrogenic effects of antibiotic medications. One of the most common indications for probiotics is for prevention of antibiotic-associated diarrhea. Clinically, different probiotic strains have demonstrated the ability to prevent AAD; however, the mechanism of action behind this effect has not been elucidated. Data from several studies suggest that antibiotic-induced disruption of commensal bacteria in the colon results in a significant (up to 50%) reduction in short chain fatty acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting in AAD. Probiotics have been shown to ameliorate a variety of gastrointestinal disease states and thus, the study investigators hypothesize that administration of a probiotic yogurt will protect against the development of AAD.


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 of the R61 phase (N=60) 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. 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. The secondary aim will be to determine the ability of BB-12 to impact antibiotic-induced disruption of the gut microbiota with 16S (16 Svedberg) ribosomal ribonucleic acid (rRNA) profiling. 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. 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.


Recruitment information / eligibility

Status Completed
Enrollment 66
Est. completion date January 8, 2020
Est. primary completion date January 8, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: 1. Has the ability to read, speak, and write in English 2. Has refrigerator (for proper storage of the study yogurt) 3. Has reliable telephone access 4. Is between ages of 18-65 years 5. Agree to refrain from eating yogurts, yogurt drinks, and other foods specified in the provided What Not to Eat list 6. Agree to collect stool samples and participate in follow-up calls as specified Exclusion Criteria: 1. Diabetes or asthma that requires medication 2. Allergy to strawberry 3. Active diarrhea (three or more loose stools per day for two consecutive days) 4. Any gastrointestinal (or digestive tract) medications, i.e. medicines for irritable bowel syndrome, gastroesophageal (acid) reflux disease, inflammatory bowel disease, etc. 5. History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic 6. History of gastrointestinal surgery or disease 7. Lactose intolerance that prevents participant from eating yogurt 8. Allergy to milk-protein 9. Allergy to any component of the product or the yogurt vehicle 10. Allergy to penicillin or cephalosporin class antibiotics 11. Allergy to any of the following medications: a) Penicillin; b) Erythromycin; c) Tetracycline; d) Trimethoprim; e) Ciprofloxacin 12. Women who are breastfeeding, pregnant, or planning to become pregnant during the study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Biological:
BB-12
Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt
Other:
Control
Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)

Locations

Country Name City State
United States Georgetown University Department of Family Medicine Washington District of Columbia

Sponsors (3)

Lead Sponsor Collaborator
Georgetown University National Center for Complementary and Integrative Health (NCCIH), University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (1)

Merenstein D, Fraser CM, Roberts RF, Liu T, Grant-Beurmann S, Tan TP, Smith KH, Cronin T, Martin OA, Sanders ME, Lucan SC, Kane MA. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Hu — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The first of two baseline samples was collected from each subject at the time of enrollment (pre run-in) before a 30-day run-in period in which the consumption of dietary probiotics was stopped. A higher index indicates more diversity and a lower index indicates less diversity. day 0 (pre run-in), 7, 14, 21, 30
Other Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The second baseline sample was collected from each subject after a 30-day run-in period in which the consumption of dietary probiotics was stopped (post run-in). A higher index indicates more diversity and a lower index indicates less diversity. day 0 (post run-in), 7, 14, 21, 30
Other Bray-Curtis Dissimilarity Community divergence over time with respect to the baseline sample (post run-in, day 0) day 0, 7, 14, 21, 30
Other Change in Diarrhea/Stool Frequency Change in diarrhea/stool frequency from baseline day 7, 14, 21, 30
Primary Level of Fecal Short-chain Fatty Acid (SCFA) Acetate Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate day 0 (post run-in), 7, 14, 21, 30
Secondary Level of Fecal SCFA Propionate Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate day 0 (post run-in), 7, 14, 21, 30
Secondary Level of Fecal SCFA Butyrate Level of fecal short-chain fatty acid butyrate (µM) after administration of amoxicillin clavulanate day 0 (post run-in), 7, 14, 21, 30
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