Antibiotic-Associated Diarrhea and the Role of Microorganisms in the Gut

Antibiotic-associated Diarrhea Clinical Trial

Official title: Antibiotic-associated Gastrointestinal Side Effects and the Role of the Gut Microbiome

Status Completed

Clinical 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). 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Antibiotic-associated Diarrhea
• Diarrhea

• NCT number: NCT04156555
• Study type: Interventional
• Source: Singapore General Hospital
• Status: Completed
• Phase: Phase 4
• Start date: August 1, 2019
• Completion date: October 26, 2022