MicrobiotaNCT03098485
Healthy Patients & Effect of Antibiotics
A study testing Levofloxacin, Azithromycin and Cefpodoxime in people with Microbiota and Anti-bacterial Agents, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The objective of this study is to evaluate the impact of antimicrobial (antibiotic) exposures on the microbiome in healthy adults, specifically during and after usual courses of the antimicrobials used to treat community acquired pneumonia (CAP). Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Microbiota, Anti-bacterial Agents
- What is being tested?
- Levofloxacin, Azithromycin and Cefpodoxime
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 30 Aug 2022
- Phase
- Interventional
- 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 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults ages 21-60 residing in the St. Louis, Missouri, USA metropolitan area
Who cannot join
- History of allergic reaction to study antimicrobial(s)
- Contraindication(s) to study antimicrobial(s)
- Inability to provide regular stool samples
- Any non-topical antimicrobial exposure in previous 6 months
- Tube feeds as primary source of nutrition in previous 6 months
- Pregnant or risk of becoming pregnant during study period
Show all 15Show fewer
- Breastfeeding during study period
- Gastroenteritis in last 3 months
- Any non-elective hospitalization in the previous 12 months
- Incontinent of stool
- Known colonization with an MDRO
- Anticipated change in diet or medications during study period
- Elective surgery during study period
- History of an intestinal disorder
- Inability to provide written, informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Prospective Study Characterizing Fecal Microbiome Disruptions During and After Receipt of Antimicrobials
The objective of this study is to evaluate the impact of antimicrobial (antibiotic) exposures on the microbiome in healthy adults, specifically during and after usual courses of the antimicrobials used to treat community acquired pneumonia (CAP). Pneumonia is a lung infection, and community-acquired pneumonia is pneumonia that develops outside of a healthcare facility (i.e., in the community). A microbiome is a the community of microorganisms living in a particular location, such as the gut or the mouth. Disruptions to a person's microbiome may reduce his/her "colonization resistance" (resistance to colonization with pathogenic microorganisms) and make him/her more susceptible to multidrug resistant organism (MDRO) colonization and infection.
To study changes in the microbiome, the investigators will recruit 20 healthy adult volunteers and obtain fecal, salivary, skin, and urine specimens at multiple time points before, during, and after administration of antimicrobials. Participants will be randomized to one of 4 antimicrobial regimens, all of which are FDA-approved for treatment of community-acquired pneumonia. Stool specimens will be analyzed via stool culture and genetic sequencing, and all remaining specimens will be frozen and used to create a biospecimen repository for future analysis. The rationale for using healthy volunteers (instead of patients already prescribed antibiotics by their physicians) is because the human microbiome is very complex and can be affected by a variety of medical conditions and other medications. In addition, the presence or absence of patient-specific factors means people with infections may not be prescribed the specific courses of antibiotics the investigators are trying to study. Studying the effect of antibiotics on healthy volunteers will provide baseline data that are more applicable to the population at large.
Read the detailed description
Each year, antimicrobial resistance causes over two million infections and 23,000 deaths in the US alone, representing a critical global public health issue. Some of the most feared multidrug resistant organisms (MDROs) include Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL), MDRO Acinetobacter, and MDRO Pseudomonas aeruginosa; there are few antimicrobials effective against these MDROs, and available antimicrobials often have rate-limiting toxicities. The major risk factor for MDRO colonization and subsequent MDRO infections is exposure to antimicrobials. The use of antimicrobials has been associated with an altered and often less diverse composition of the fecal microbiome, and expansion of the resistome. A "healthy" microbiome provides "colonization resistance" against potentially pathogenic bacteria; antimicrobials disrupt this protective community, providing selective pressure that favors MDRO colonization, persistence, and transmission to others.
Methods to proactively prevent MDRO colonization, rather than reliance on reactive approaches to this problem, are urgently needed. Antimicrobial stewardship is a key component of MDRO prevention efforts; however, there is no method to determine which antimicrobials cause the greatest degree of microbiome disruption. A better understanding of exactly how antimicrobials alter the microbiome is necessary to optimally guide future MDRO prevention efforts and antimicrobial stewardship. The development of microbiome disruption indices (MDIs) would help characterize the risk associated with specific antimicrobials, and can be used during antimicrobial development, patient monitoring while on antimicrobials, and to facilitate infection prevention efforts to contain MDRO spread. Additionally, MDIs can be used as an alert when microbiome disruptions reach a critical level and MDRO colonization is imminent. At that point, interventions to restore the microbiome could be implemented.
Community-acquired pneumonia (CAP) is one of the leading causes of death in the United States, with an estimated >900,000 cases each year in adults age 65 and older. Large amounts of antimicrobials are used in treating patients with CAP because the disease is relatively common. A better understanding of the effect of CAP antimicrobial treatment on the microbiome could result in improved treatment options for patients with CAP and protect CAP patients from colonization or infection with MDROs.
- Conditions
- Microbiota, Anti-bacterial Agents
- Being tested
- Levofloxacin, Azithromycin, Cefpodoxime
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevofloxacinDrug
Also called Levaquin, Quixin, Iquix
5 days of levofloxacin administration
AzithromycinDrug
Also called Zithromax, AzaSite, Zmax
5 days of azithromycin administration
CefpodoximeDrug
Also called Vantin
5 days of cefpodoxime administration
| Study group | Role | What they receive |
|---|---|---|
| Levofloxacin | Experimental | 1 750mg tab of levofloxacin by mouth for 5 days Receives: Drug: Levofloxacin |
| Azithromycin | Experimental | 1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days) Receives: Drug: Azithromycin |
| Cefpodoxime | Experimental | 200mg tab by mouth twice per day for 5 days Receives: Drug: Cefpodoxime |
| Azithromycin and cefpodoxime | Experimental | Azithromycin: 1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days)
Cefpodoxime: 200mg tab by mouth twice per day for 5 days Receives: Drug: Azithromycin; Drug: Cefpodoxime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of Microbial Disruption: Number of Patients With Recovery of Bacterial Species Richness at 185 Days Post-antibiotics
The degree of microbial disruption will be defined by recovery of bacterial species richness (number of species) after antibiotics.
Measured: Decrease from baseline (7 days prior to antibiotics) in microbial diversity at 185 days post-antibiotics
Degree of Microbial Disruption: Number of Patients With Increase in Antibiotic Resistance Genes at 185 Days Post-antibiotics
The degree of microbiome disruptions will be defined by an increase in the number of antibiotic resistance genes after antibiotics compared to baseline.
Measured: Increase from baseline (7 days prior to antibiotics) in antibiotic resistance genes at 185 days post-antibiotics
Degree of Microbial Disruption: Number of Patients With Continued Microbial Disruption at 185 Days Post-antibiotics
The degree of microbiome disruptions will be defined by continuing microbial disruption, as measured by Bray-Curtis dissimilarity, post-antibiotics compared to baseline.
Measured: Persistent disruption from baseline (7 days prior to antibiotics) in microbial composition at 185 days post-antibiotics
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study startJan 2017
- Primary completion30 Aug 2022
- Study completion30 Aug 2022
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.
- Other trials for MicrobiotaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennie H. Kwon, DO, MSCI, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098485
- Sponsor's protocol ID
- 201610071
- Status last verified
- Oct 2022
- First submitted
- 11 Jan 2017
- Last updated
- 10 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Summarized metagenomics sequence data will be made available through public repositories at the time of manuscript publication.
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study Characterizing Fecal Microbiome Disruptions During and After Receipt of Antimicrobials
- ClinicalTrials.gov ID
- NCT03098485
- Acronym / sponsor ID
- 201610071
- Conditions
- Microbiota, Anti-bacterial Agents
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 30 Aug 2022 (actual)
- First posted
- 31 Mar 2017 (actual)
- Results
- Posted 10 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the impact of antimicrobial (antibiotic) exposures on the microbiome in healthy adults, specifically during and after usual courses of the antimicrobials used to treat community acquired pneumonia (CAP). Pneumonia is a lung infection, and community-acquired pneumonia is pneumonia that develops outside of a healthcare facility (i.e., in the community). A microbiome is a the community of microorganisms living in a particular location, such as the gut or the mouth. Disruptions to a person's microbiome may reduce his/her "colonization resistance" (resistance to colonization with pathogenic microorganisms) and make him/her more susceptible to multidrug resistant organism (MDRO) colonization and infection.
To study changes in the microbiome, the investigators will recruit 20 healthy adult volunteers and obtain fecal, salivary, skin, and urine specimens at multiple time points before, during, and after administration of antimicrobials. Participants will be randomized to one of 4 antimicrobial regimens, all of which are FDA-approved for treatment of community-acquired pneumonia. Stool specimens will be analyzed via stool culture and genetic sequencing, and all remaining specimens will be frozen and used to create a biospecimen repository for future analysis. The rationale for using healthy volunteers (instead of patients already prescribed antibiotics by their physicians) is because the human microbiome is very complex and can be affected by a variety of medical conditions and other medications. In addition, the presence or absence of patient-specific factors means people with infections may not be prescribed the specific courses of antibiotics the investigators are trying to study. Studying the effect of antibiotics on healthy volunteers will provide baseline data that are more applicable to the population at large.
Detailed description
Each year, antimicrobial resistance causes over two million infections and 23,000 deaths in the US alone, representing a critical global public health issue. Some of the most feared multidrug resistant organisms (MDROs) include Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL), MDRO Acinetobacter, and MDRO Pseudomonas aeruginosa; there are few antimicrobials effective against these MDROs, and available antimicrobials often have rate-limiting toxicities. The major risk factor for MDRO colonization and subsequent MDRO infections is exposure to antimicrobials. The use of antimicrobials has been associated with an altered and often less diverse composition of the fecal microbiome, and expansion of the resistome. A "healthy" microbiome provides "colonization resistance" against potentially pathogenic bacteria; antimicrobials disrupt this protective community, providing selective pressure that favors MDRO colonization, persistence, and transmission to others.
Methods to proactively prevent MDRO colonization, rather than reliance on reactive approaches to this problem, are urgently needed. Antimicrobial stewardship is a key component of MDRO prevention efforts; however, there is no method to determine which antimicrobials cause the greatest degree of microbiome disruption. A better understanding of exactly how antimicrobials alter the microbiome is necessary to optimally guide future MDRO prevention efforts and antimicrobial stewardship. The development of microbiome disruption indices (MDIs) would help characterize the risk associated with specific antimicrobials, and can be used during antimicrobial development, patient monitoring while on antimicrobials, and to facilitate infection prevention efforts to contain MDRO spread. Additionally, MDIs can be used as an alert when microbiome disruptions reach a critical level and MDRO colonization is imminent. At that point, interventions to restore the microbiome could be implemented.
Community-acquired pneumonia (CAP) is one of the leading causes of death in the United States, with an estimated >900,000 cases each year in adults age 65 and older. Large amounts of antimicrobials are used in treating patients with CAP because the disease is relatively common. A better understanding of the effect of CAP antimicrobial treatment on the microbiome could result in improved treatment options for patients with CAP and protect CAP patients from colonization or infection with MDROs.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Levofloxacin | Experimental | Drug: Levofloxacin1 750mg tab of levofloxacin by mouth for 5 days |
| Azithromycin | Experimental | Drug: Azithromycin1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days) |
| Cefpodoxime | Experimental | Drug: Cefpodoxime200mg tab by mouth twice per day for 5 days |
| Azithromycin and cefpodoxime | Experimental | Drug: Azithromycin, Drug: CefpodoximeAzithromycin: 1 500mg tab by mouth on day 1, then 1 250 mg tab per day by mouth for 4 days (total 5 days) Cefpodoxime: 200mg tab by mouth twice per day for 5 days |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy adults ages 21-60 residing in the St. Louis, Missouri, USA metropolitan area
Key exclusion criteria (15 listed)
- History of allergic reaction to study antimicrobial(s)
- Contraindication(s) to study antimicrobial(s)
- Inability to provide regular stool samples
- Any non-topical antimicrobial exposure in previous 6 months
- Tube feeds as primary source of nutrition in previous 6 months
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 |
|---|---|---|
| LevofloxacinAlso: Levaquin, Quixin, Iquix5 days of levofloxacin administration | Drug | Levofloxacin |
| AzithromycinAlso: Zithromax, AzaSite, Zmax5 days of azithromycin administration | Drug | Azithromycin, Azithromycin and cefpodoxime |
| CefpodoximeAlso: Vantin5 days of cefpodoxime administration | Drug | Azithromycin and cefpodoxime, Cefpodoxime |
Primary outcome
Degree of Microbial Disruption: Number of Patients With Recovery of Bacterial Species Richness at 185 Days Post-antibiotics
Time frame: Decrease from baseline (7 days prior to antibiotics) in microbial diversity at 185 days post-antibiotics
The degree of microbial disruption will be defined by recovery of bacterial species richness (number of species) after antibiotics.
Degree of Microbial Disruption: Number of Patients With Increase in Antibiotic Resistance Genes at 185 Days Post-antibiotics
Time frame: Increase from baseline (7 days prior to antibiotics) in antibiotic resistance genes at 185 days post-antibiotics
The degree of microbiome disruptions will be defined by an increase in the number of antibiotic resistance genes after antibiotics compared to baseline.
Degree of Microbial Disruption: Number of Patients With Continued Microbial Disruption at 185 Days Post-antibiotics
Time frame: Persistent disruption from baseline (7 days prior to antibiotics) in microbial composition at 185 days post-antibiotics
The degree of microbiome disruptions will be defined by continuing microbial disruption, as measured by Bray-Curtis dissimilarity, post-antibiotics compared to baseline.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Summarized metagenomics sequence data will be made available through public repositories at the time of manuscript publication.
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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.
Jennie H. Kwon, DO, MSCI principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Levofloxacin, Azithromycin and Cefpodoxime in people with Microbiota and Anti-bacterial Agents, run by Washington University School of Medicine 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 1 inclusion and 15 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 10 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 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2022). 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?
Degree of Microbial Disruption: Number of Patients With Recovery of Bacterial Species Richness at 185 Days Post-antibiotics (time frame: Decrease from baseline (7 days prior to antibiotics) in microbial diversity at 185 days post-antibiotics). The study lists 3 primary outcomes in all. 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 10 Nov 2022.