Antibiotic-associated DiarrheaEarly Phase 1YOBIOTICNCT03755765
Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics
A Early Phase 1 study testing Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet and BB-12 in people with Antibiotic-associated Diarrhea, run by Georgetown University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Antibiotic-associated Diarrhea
- What is being tested?
- Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet and BB-12
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2019to 8 Jan 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Has the ability to read, speak, and write in English
- Has 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 What Not to Eat list
- Agree to collect stool samples and participate in follow-up calls as specified
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown University Department of Family Medicine
Washington D.C., District of Columbia, 20007
About this study
Official title: Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics
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.
Read the 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 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.
- Conditions
- Antibiotic-associated Diarrhea
- Being tested
- Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet, BB-12, Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral TabletDrug
Also called Augmentin
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
BB-12Biological
Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt
ControlOther
Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet Receives: Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Other: Control |
| BB-12 | Experimental | Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet Receives: Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Biological: BB-12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of Fecal Short-chain Fatty Acid (SCFA) Acetate
Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate
Measured: day 0 (post run-in), 7, 14, 21, 30
Secondary outcomes (2)
Level of Fecal SCFA Propionate
Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate
Measured: day 0 (post run-in), 7, 14, 21, 30
Level of Fecal SCFA Butyrate
Level of fecal short-chain fatty acid butyrate (μM) after administration of amoxicillin clavulanate
Measured: day 0 (post run-in), 7, 14, 21, 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2018
- Study start23 Jul 2019
- Primary completion8 Jan 2020
- Study completion8 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antibiotic-associated DiarrheaStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), University of Maryland, Baltimore
- Responsible party
- Principal investigator, Daniel Merenstein, Georgetown University
- Investigators
- Daniel Merenstein, MD, Principal investigator, Georgetown UniversityClaire Fraser, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03755765
- Sponsor's protocol ID
- 2018-0736
- Other IDs
- 1R61AT009622-01A1
- Acronym
- YOBIOTIC
- Status last verified
- Feb 2023
- First submitted
- 18 Nov 2018
- Last updated
- 17 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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 Human Fecal Microbiome. Nutrients. 2021 Aug 17;13(8):2814. doi: 10.3390/nu13082814.
PubMed 34444974
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics
- ClinicalTrials.gov ID
- NCT03755765
- Acronym / sponsor ID
- YOBIOTIC / 2018-0736
- Conditions
- Antibiotic-associated Diarrhea
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), University of Maryland, Baltimore
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- 8 Jan 2020 (actual)
- Study completion
- 8 Jan 2020 (actual)
- First posted
- 28 Nov 2018 (actual)
- Results
- Posted 17 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet, Other: ControlYogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet |
| BB-12 | Experimental | Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet, Biological: BB-12Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Has the ability to read, speak, and write in English
- Has 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 What Not to Eat list
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amoxicillin-Clavulanate 875 Mg-125 Mg Oral TabletAlso: AugmentinAmoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet | Drug | BB-12, Control |
| BB-12Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt | Biological | BB-12 |
| ControlYogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) | Other | Control |
Primary outcome
Level of Fecal Short-chain Fatty Acid (SCFA) Acetate
Time frame: day 0 (post run-in), 7, 14, 21, 30
Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate
2 secondary outcomes
Level of Fecal SCFA Propionate
Time frame: day 0 (post run-in), 7, 14, 21, 30
Level of Fecal SCFA Butyrate
Time frame: day 0 (post run-in), 7, 14, 21, 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34444974Merenstein 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 Human Fecal Microbiome. Nutrients. 2021 Aug 17;13(8):2814. doi: 10.3390/nu13082814.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Merenstein, MD principal investigator
Georgetown University
Claire Fraser, PhD principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet and BB-12 in people with Antibiotic-associated Diarrhea, run by Georgetown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of Fecal Short-chain Fatty Acid (SCFA) Acetate (time frame: day 0 (post run-in), 7, 14, 21, 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03755765, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2023.