REMBRANDT: REcovery of the MicroBiome fRom Antibiotics for Dental implanTs

NCT ID: NCT05622721

Last Updated: 2025-02-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-30
• Study Completion Date: 2026-05-01

Brief Summary

Antimicrobial therapy can lead to disruption of the gut microbiome and infection with Clostridioides difficile, a disease associated with high morbidity and mortality, particularly among the elderly. Drawing on observations that pet ownership and close contact with pets are protective against colonization with C. difficile and recurrence of C. difficile infection, the proposed study will test the hypothesis that microbiota that provide colonization resistance against C. difficile are shared between patients and their pets and that pet contact can mitigate antimicrobial-associated gut dysbiosis and the risk of C. difficile infection. This study will further define epidemiologic and pathophysiologic characteristics of C. difficile infection and gut microbiome dysbiosis that could enhance therapeutic options for these conditions, potentially through non-invasive interventions involving animal contact.

Detailed Description

Clostridioides difficile infection (CDI) is one of the most common causes of healthcare-associated infectious diarrhea and results in significant morbidity and mortality. CDI occurs when the native gut microbiome is disrupted, most often following antimicrobial therapy, and the consequent dysbiosis results in a decrease in microbial diversity, changes in abundance of certain bacterial taxa, and loss of colonization resistance against C. difficile. Restoration of a "functionally intact" gut microbiome is critical to clearing C. difficile, and inadequate restoration can lead to recurrent CDI. The recovery of the gut microbiome from dysbiosis is poorly understood, and factors associated with having and re-gaining a providing colonization resistance against C. difficile are not well known. While animal reservoirs can serve as potential sources of pathogenic bacteria, studies by the candidate and other investigators found that pet ownership protects against colonization and re-infection with C. difficile. Moreover, microbiota are shared between pets and their owners, and the microbiomes of pets contain bacterial taxa that provide colonization resistance against C. difficile. Based on these data, the proposed research will 1) test the hypothesis that the observed protective effects of pet ownership are due to sharing of microbiota that provide colonization resistance against C. difficile between pets and owners; 2) determine whether pet contact mitigates antimicrobial-associated disruption of the gut microbiome and enhances its recovery; and 3) assess whether pet contact decreases the likelihood of colonization and infection with C. difficile following antimicrobial therapy. This will be accomplished though longitudinal sampling of the gut microbiome within the patient/pet unit among patients receiving prophylactic antimicrobials for non-enteric indications (dental implants).

The study will further define epidemiologic and pathophysiologic characteristics of CDI that could enhance therapeutic options for this disease. The underlying premise that animals are a source of protective microbiota rather than a reservoir of C. difficile represents a paradigm shift in CDI epidemiology that may identify animal contact as a novel microbiome-based form of therapy.

Conditions

Dysbiosis; Clostridium Difficile; Pet-Human Bonding; Antibiotic-Associated Colitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pet owner

Pet owners

No interventions assigned to this group

Non pet owner

Non pet owners

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older.
• Receiving a dental implant.
• Ability to understand study procedures and to comply with them for the entire length of the study.

Exclusion Criteria

• Antimicrobial therapy or hospitalization in the prior three months;
• Any gastrointestinal illness or underlying pathology (e.g., Inflammatory Bowel Disease, gastric ulceration)
• Sustained diarrheal disease (i.e., at least 3 episodes of loose or watery stool per day for 3 or more days) in the prior 3 months;
• Prior history of CDI in the prior year;
• Immunomodulating medication (e.g., tumor necrosis factor inhibitors or systemic steroids) or conditions (e.g., leukemia)
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Laurel Redding

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laurel Redding, VMD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

The Robert Schattner Center, University of Pennsylvania, School of Dental Medicine

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Laurel Redding, VMD, PhD

Role: CONTACT

lredding@upenn.edu

6109256307

Facility Contacts

Marta Gabinsky

Role: primary

mgabi@upenn.edu

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1K23AI163351-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

844131

Identifier Type: -

Identifier Source: org_study_id