Effect of Antibiotics on Urinary Microbiome

October 28, 2021 updated by: Johns Hopkins University

Effect of Antibiotics on Urinary Microbiome: Randomized Trial

Planning to study urine microbiota at baseline and after administration of bactrim antibiotics in healthy volunteers. Will intermittently collect voided urine specimens for 16 s DNA analysis over a period of 6 months after 2 weeks of bactrim or placebo.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Urinary tract infections (UTI) are the most common type of human bacterial disease, prompting more than 10 million physician office visits annually at a healthcare cost of over $1 billion dollars. Treatment of UTI is typically empiric or culture-driven antibiotics which are associated with ever increasing bacterial resistance. Over the last decade, The Human Microbiome Project has established that even 'culture-negative' urine represents a diverse ecosystem of bacteria. Despite broad use of antibiotics to cure disease for the past 90 years, the broader impact of antibiotics on typical flora are not well understood. Antibiotics are also commonly used as prophylaxis for surgical procedures in the urinary tract altering patient outcomes in unforeseen ways. Despite widespread utilization of antibiotics, the longitudinal impact on the dynamic intravesical environment remains completely unknown.

Dysbiosis in the microbiome has been suggested as a causative agent in a wide range of disease: arthritis, metabolic disorders, neurologic disease, inflammatory bowel conditions, and cancer. Yet there remains a fundamental knowledge gap regarding the short and long-term effect of antibiotics on microbiota communities. Specifically within the urinary tract, variance in baseline commensal organisms have been associated with interstitial cystitis, overactive bladder, frequent symptomatic urinary tract infection and potentially cancer development. The study of microbiota reveal pathways and mechanisms that play important roles in immunological response and health but studies typically are limited to the gut.

To address this knowledge gap, the investigators plan a placebo controlled randomized trial to test the longitudinal impact of 10 days of trimethoprim-sulfamethoxazole on the urinary microbiome in healthy adults. Data collection for individual participants will persist for a period of 6 months. The investigators hypothesize antibiotic administration contributes to a rise in bacterial resistance and directly leads to urine microbiome dysbiosis. The investigators further hypothesize the urinary microbiome does not return to baseline, with loss of certain bacteria permanent during the study period. While the investigators' study is groundbreaking and novel, the feasibility of the investigators' experimental plan has been previously demonstrated in the study of the salivary and gut microbiome. Ultimately the investigators anticipate even a single course of antibiotic treatment may increase the risk of bacterial resistance and lead to long-lasting shifts in the urinary microbiome. If confirmed, this knowledge will directly influence clinical decision making in antibiotic selection, duration, and utility.

Study Type

Interventional

Phase

  • Early Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Exclusion Criteria:

  • Diagnosed or suspected urinary tract infection in prior 6 months
  • Treated with antibiotics for any reason in prior 6 months
  • Allergy to sulfa
  • Under 18
  • Pregnant or planning to become pregnant in the next 12 months by self report (as is the clinical standard for prescribing this medication for suspected or proven UTI treatment)
  • Use indwelling or intermittent urinary hardware or implant such as supra-pubic tube or catheter
  • Neurogenic bladder
  • Baseline renal insufficiency
  • Glucose-6-phosphate dehydrogenase deficiency
  • Taking angiotensin converting enzyme
  • Angiotensin receptor blocker
  • Nursing
  • HIV/AIDS
  • On Immunosuppressant drugs
  • On Chemotherapy/Immunotherapy
  • Liver dysfunction
  • On the following medications: DOFETILIDE, METHENAMINE & LEVOMETHADYL; WARFARIN & Methotrexate; GEMIFLOXACIN, DIGOXIN, PYRIMETHAMINE, CLASS IA ANTIARRHYTHMIC AGENTS (Quinidine, procainamide, disopyramide), TRICYCLIC ANTIDEPRESSANTS (amitriptyline, desipramine, doxepin, Imipramine, nortriptyline, amoxapine, clomipramine, maprotiline, trimipramine, and protriptyline), LEUCOVORIN CALCIUM.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Participants will be recruited and enrolled. Participants will be surveyed regarding environmental, health, and behavioral practices. (Instrument 1) . Then a clean catch urine specimen will be collected. Participants will be provided with placebo to be taken twice daily. This will be considered day 0. Participants will then be instructed to take the study drug twice daily and return on Day 2, Day 5, Day 10, Day 30, and Day 180 for additional clean-catch urine specimen.
Drug: Placebo oral tablet
To study effect on urinary microbiome
Experimental: Bactrim
Participants will be recruited and enrolled. Participants will be surveyed regarding environmental, health, and behavioral practices. (Instrument 1) . Then a clean catch urine specimen will be collected. Participants will be provided with Bactrim 800/120 to take twice daily. This will be considered day 0. Participants will then be instructed to take the study drug twice daily and return on Day 2, Day 5, Day 10, Day 30, and Day 180 for additional clean-catch urine specimen.
Drug: Bactrim DS 800Mg-160Mg Tablet
To study effect on urinary microbiome
Other Names:
  • bactrim, trimethoprim sulfamethoxazole, Septra, sulfatrim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Microbiome flora number of organisms
Time Frame: At Baseline, Day 2, Day 5, Day 10, Day 30, and Day 180 of study
Analysis of 16S rRNA gene amplicon data to determine number of varied organisms (genus and species).
At Baseline, Day 2, Day 5, Day 10, Day 30, and Day 180 of study
Change in Microbiome flora percentage distribution of organisms
Time Frame: At Baseline, Day 2, Day 5, Day 10, Day 30, and Day 180 of study
Analysis of 16S rRNA gene amplicon data to determine the percent distribution of organisms (microbiologic genus and species).
At Baseline, Day 2, Day 5, Day 10, Day 30, and Day 180 of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Andrew J Cohen, MD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2023

Primary Completion (Anticipated)

February 1, 2025

Study Completion (Anticipated)

February 1, 2026

Study Registration Dates

First Submitted

December 27, 2019

First Submitted That Met QC Criteria

January 13, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Actual)

November 3, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00224835

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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