Antibiotic-associated DiarrheaPhase 4NCT04156555
Antibiotic-Associated Diarrhea and the Role of Microorganisms in the Gut
A Phase 4 study testing Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet in people with Antibiotic-associated Diarrhea, run by Singapore General Hospital at 1 site in Singapore.
Trial summary
Amoxicillin-clavulanate is an antibiotic commonly prescribed to treat a myriad of community-acquired infections. One of the most common adverse effects of amoxicillin-clavulanate is antibiotic-associated diarrhea (AAD). Read more about this study
- Who is it for?
- Ages 21 to 40 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Aug 2019to 26 Oct 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 21 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults, 21-40 years of age at time of screening
- Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
- Accessible vein for blood collection.
- Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. (e.g., completion of the subject diary, return for follow-up visits) and who are willing to make themselves available for the duration of the study, with access to a consistent means of telephone contact, which may be either at home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device (i.e. a common-use phone serving multiple rooms or apartments).
- Ability to provide informed consent
- Female subjects of non-child bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopausal subjects must have had at least 12 months of natural (spontaneous) amenorrhea.
- Female subjects of childbearing potential may be enrolled in the study if they have negative urine pregnancy tests on the day of screening and day of antibiotic administration.
- Willing to abstain from the use of probiotics or prebiotics for the duration of the study.
Who cannot join
- Underlying chronic medical illness
- History of Clostridium difficile diarrhea
- History of Inflammatory Bowel disease or any other chronic gastrointestinal tract illness
- Known drug allergy to amoxicillin-clavulanate, its components, or any other beta-lactam antibiotics.
- Presence of acute infection in the preceding 7 days or presence of a temperature ≥ 38.0°C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of first dose
- Any condition that, in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject.
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- Woman who is pregnant or breast feeding.
- Evidence of substance abuse, or previous substance abuse including alcohol
- Participation in a study involving administration of an investigational compound within the past three months, or planned participation during the duration of this study.
- Receipt of antibiotics in the past 3 months.
- Receipt of probiotics or prebiotics in the past 7 days.
- Previous history of Augmentin-associated jaundice and/or hepatic dysfunction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Antibiotic-associated Gastrointestinal Side Effects and the Role of the Gut Microbiome
Amoxicillin-clavulanate is an antibiotic commonly prescribed to treat a myriad of community-acquired infections. One of the most common adverse effects of amoxicillin-clavulanate is antibiotic-associated diarrhea (AAD). Studies have shown that administration of antibiotics can cause disruption and changes in the diversity of microorganisms within the gut (gut microbiome), with overgrowth of "harmful" bacteria as a possible driver for AAD. How antibiotics specifically affect the gut microbiome to cause AAD in humans, however, remains unknown. The overall goal of the study is to characterize the changes in the gut microbiome over time, in subjects who develop AAD after antibiotic ingestion, and to further demonstrate that resolution of AAD is due to return of "friendly, anti-diarrhea bacteria". The study investigators will also measure the proteins produced by the gut bacteria, as a potential tool to help predict which individuals are at risk of AAD.
The investigators plan to recruit 30 healthy adult volunteers who will receive 3 days of oral amoxicillin-clavulanate, a very commonly prescribed antibiotic. Stool and blood samples will be collected throughout the study up to 28 days after antibiotic administration. The study investigators will measure and compare the changes in the gut microbiome and metabolic responses in order to identify the relationship between these changes and the onset of AAD. The results from this study will not only yield important scientific knowledge about the pathogenesis of AAD, but will also provide new leads to understand the interplay between the gut microbiome, immune-metabolism and AAD. These findings also have the potential to identify clinically important biomarkers to allow pre-identification of individuals at risk of AAD. If successful, this study could pave the way for personalized medicine for management of bacterial infections. This will help to prevent premature stoppage of antibiotic therapy due to diarrhea side effects, and reduce the risk of bacterial resistance from suboptimal treatment.
Read the detailed description
All eligible subjects will proceed to Day 0, where they will receive study drug amoxicillin-clavulanate 1g twice a day for 3 days. Prior to administration of study drug on Day 0, stool sample and blood will be collected for microbiome and metabolomics \& gene expression analysis respectively. Urine pregnancy test (for females subjects of child-bearing potential) will be performed prior to study drug administration. Baseline physical examination and vital signs will be done as well.
Subsequently, stool and blood samples will be collected on day 1, day 2, day 3, day 7, day 14, and day 28. Physical examination, vital signs, and review of adverse events will be done at each of the visits as well.
Volunteers will be monitored for symptoms of AAD throughout this period. All study subjects will be asked to keep a standardised patient diary up to day 28 or until symptom resolution whichever is longer. All other potential AEs will also be solicited for throughout study period. Subjects who develop AAD will be graded according to CTCAE version 5.0 criteria for AEs. The study drug Augmentin will be discontinued in subjects who develop AAD, defined as a passage of loose or watery stool at least 3 times in a 24-hour period. Management of AAD is at the discretion of the study team PI and co-Is, guided by severity and clinical indication for intervention. All medication prescribed for the management of AAD or other AEs will be documented in the medication/concomitant medication clinical record form.
- Conditions
- Antibiotic-associated Diarrhea
- Being tested
- Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
- Keywords
- amoxicillin-clavulanate, diarrhea, Gut microbiome
- Medical subject headings
- Diarrhea
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, Moxiclav
Oral amoxicillin-clavulanate 1 g twice a day for total of 6 doses
| Study group | Role | What they receive |
|---|---|---|
| Study drug | Experimental | Not described Receives: Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Operational taxonomic unit counts of bacterial species in the gut microbiota
Change from baseline in operational taxonomic unit counts of bacterial species in the gut microbiota of subjects who develop AAD compared to those who do not develop AAD after a 3 day course of oral Augmentin
Measured: 28 days
Secondary outcomes (1)
Diversity index of gut microbiome
Change from baseline in diversity index of gut microbiota of subjects who develop AAD compared to those who do not develop AAD after a 3 day course of oral Augmentin.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start1 Aug 2019
- Primary completion26 Oct 2022
- Study completion26 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antibiotic-associated DiarrheaStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe 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
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shirin Kalimuddin, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04156555
- Sponsor's protocol ID
- AAD-MB-01
- Other IDs
- AM/CT003/2018 (SRDUKAMR18C3)
- Status last verified
- Oct 2022
- First submitted
- 28 Oct 2019
- Last updated
- 1 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antibiotic-associated Gastrointestinal Side Effects and the Role of the Gut Microbiome
- ClinicalTrials.gov ID
- NCT04156555
- Acronym / sponsor ID
- AAD-MB-01
- Conditions
- Antibiotic-associated Diarrhea
- Keywords
- amoxicillin-clavulanate, diarrhea, Gut microbiome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 26 Oct 2022 (actual)
- Study completion
- 26 Oct 2022 (actual)
- First posted
- 7 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Amoxicillin-clavulanate is an antibiotic commonly prescribed to treat a myriad of community-acquired infections. One of the most common adverse effects of amoxicillin-clavulanate is antibiotic-associated diarrhea (AAD). Studies have shown that administration of antibiotics can cause disruption and changes in the diversity of microorganisms within the gut (gut microbiome), with overgrowth of "harmful" bacteria as a possible driver for AAD. How antibiotics specifically affect the gut microbiome to cause AAD in humans, however, remains unknown. The overall goal of the study is to characterize the changes in the gut microbiome over time, in subjects who develop AAD after antibiotic ingestion, and to further demonstrate that resolution of AAD is due to return of "friendly, anti-diarrhea bacteria". The study investigators will also measure the proteins produced by the gut bacteria, as a potential tool to help predict which individuals are at risk of AAD.
The investigators plan to recruit 30 healthy adult volunteers who will receive 3 days of oral amoxicillin-clavulanate, a very commonly prescribed antibiotic. Stool and blood samples will be collected throughout the study up to 28 days after antibiotic administration. The study investigators will measure and compare the changes in the gut microbiome and metabolic responses in order to identify the relationship between these changes and the onset of AAD. The results from this study will not only yield important scientific knowledge about the pathogenesis of AAD, but will also provide new leads to understand the interplay between the gut microbiome, immune-metabolism and AAD. These findings also have the potential to identify clinically important biomarkers to allow pre-identification of individuals at risk of AAD. If successful, this study could pave the way for personalized medicine for management of bacterial infections. This will help to prevent premature stoppage of antibiotic therapy due to diarrhea side effects, and reduce the risk of bacterial resistance from suboptimal treatment.
Detailed description
All eligible subjects will proceed to Day 0, where they will receive study drug amoxicillin-clavulanate 1g twice a day for 3 days. Prior to administration of study drug on Day 0, stool sample and blood will be collected for microbiome and metabolomics \& gene expression analysis respectively. Urine pregnancy test (for females subjects of child-bearing potential) will be performed prior to study drug administration. Baseline physical examination and vital signs will be done as well.
Subsequently, stool and blood samples will be collected on day 1, day 2, day 3, day 7, day 14, and day 28. Physical examination, vital signs, and review of adverse events will be done at each of the visits as well.
Volunteers will be monitored for symptoms of AAD throughout this period. All study subjects will be asked to keep a standardised patient diary up to day 28 or until symptom resolution whichever is longer. All other potential AEs will also be solicited for throughout study period. Subjects who develop AAD will be graded according to CTCAE version 5.0 criteria for AEs. The study drug Augmentin will be discontinued in subjects who develop AAD, defined as a passage of loose or watery stool at least 3 times in a 24-hour period. Management of AAD is at the discretion of the study team PI and co-Is, guided by severity and clinical indication for intervention. All medication prescribed for the management of AAD or other AEs will be documented in the medication/concomitant medication clinical record form.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study drug | Experimental | Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy adults, 21-40 years of age at time of screening
- Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
- Accessible vein for blood collection.
- Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. (e.g., completion of the subject diary, return for follow-up visits) and who are willing to make themselves available for the duration of the study, with access to a consistent means of telephone contact, which may be either at home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device (i.e. a common-use phone serving multiple rooms or apartments).
- Ability to provide informed consent
Key exclusion criteria (12 listed)
- Underlying chronic medical illness
- History of Clostridium difficile diarrhea
- History of Inflammatory Bowel disease or any other chronic gastrointestinal tract illness
- Known drug allergy to amoxicillin-clavulanate, its components, or any other beta-lactam antibiotics.
- Presence of acute infection in the preceding 7 days or presence of a temperature ≥ 38.0°C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of first dose
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: Augmentin, MoxiclavOral amoxicillin-clavulanate 1 g twice a day for total of 6 doses | Drug | Study drug |
Primary outcome
Operational taxonomic unit counts of bacterial species in the gut microbiota
Time frame: 28 days
Change from baseline in operational taxonomic unit counts of bacterial species in the gut microbiota of subjects who develop AAD compared to those who do not develop AAD after a 3 day course of oral Augmentin
1 secondary outcome
Diversity index of gut microbiome
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
- Individual participant dataSharing planned: No
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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.
Shirin Kalimuddin principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet in people with Antibiotic-associated Diarrhea, run by Singapore General Hospital at 1 site in Singapore.
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 8 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 1 Nov 2022. 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 Singapore. 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. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Operational taxonomic unit counts of bacterial species in the gut microbiota (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Nov 2022.