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

NCT04156555 | Completed Phase 4

• 2 other identifiers: AAD-MB-01AM/CT003/2018 (SRDUKAMR18C3)
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Antibiotic-associated Diarrhea

Keywords

amoxicillin-clavulanate; diarrhea; Gut microbiome

Outcome Measures

Primary Outcomes (1)

• 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

  28 days

Secondary Outcomes (1)

• Diversity index of gut microbiome

  28 days

Study Arms (1)

Study drug

EXPERIMENTAL

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

Interventions

Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet DRUG

Oral amoxicillin-clavulanate 1 g twice a day for total of 6 doses

Also known as: Augmentin, Moxiclav

Study drug

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital

Singapore, 169074, Singapore

Location

MeSH Terms

Conditions

Diarrhea

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Shirin Kalimuddin

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 7, 2019
• Study Start: August 1, 2019
• Primary Completion: October 26, 2022
• Study Completion: October 26, 2022
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)