Effect of Antibiotics on Enteric Neurons and Glia

NCT05834036 | Completed Phase 4 Results FDA Drug

• 1 other identifier: YAL-1038
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The interactions between bacteria and their products with the intestinal tissue are important for maintaining a healthy and balanced system. Alterations in gut bacteria communities have been associated with various human pathologies. The investigators have found that mice treated with short and long-term antibiotics exhibit a transient yet profound loss of neurons in the more superficial submucosal and deeper muscularis plexi in the intestine accompanied by slow motility. Glia cells also depend on microbiota for their maintenance. In humans, antibiotic use has been associated with disorders of gut-brain interactions (DGBI) such as irritable bowel syndrome however whether there are changes in the enteric neurons and glia cells remain unknown. Therefore, the investigators propose to further characterize the neurons and glia populations in the human distal colon after a single antibiotic course. This study will reveal glia and neuronal subtypes that are susceptible to changes in the bacteria populations and depend on microbial products for their maintenance. These findings will guide future DGBI studies to ascertain the physiological effects that such loss has on intestinal healthy balance.

Conditions

Antibiotic Enterocolitis

Keywords

Glia; Enteric Neurons

Outcome Measures

Primary Outcomes (2)

• Change in Mean Number of Colonic Submucosal Neurons/mm^2 in the Colon After Antibiotic Treatment

  Change in the mean number of colonic submucosal neurons counted per mm\^2 (+/- standard deviation) after antibiotics treatment compared to pre-treatment baseline.

  7 days

• Change in Mean Number of Colonic Submucosal Glia/mm^2 in the Colon After Treatment With Antibiotics

  Change in mean number of colonic submucosal glia counted per mm\^2 (+/- standard deviation) after antibiotics treatment compared to pretreatment baseline.

  7 days

Secondary Outcomes (2)

• Changes in Gene Expression in Submucosal Neurons

  7 days

• Changes in Gene Expression in Submucosal Glia

  7 days

Study Arms (1)

Healthy Controls

EXPERIMENTAL

Healthy controls

Drug: Amoxicillin Oral Capsule

Interventions

Amoxicillin Oral Capsule DRUG

Amoxicillin 875mg every 12 hours for 7 days.

Healthy Controls

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old of different sex and races.

You may not qualify if:

• Allergy to penicillin, amoxicillin, augmentin, ampicillin, and other antibiotics in the penicillin family
• Pregnancy or fertility treatments
• Usage of antibiotics, antifungals or antivirals within three months prior to participation
• Change in dietary habits within the last three months prior to participation such as transitioning from high fat western diet to primarily plant based diet, initiation of ketogenic, paleo or any other weight loss regimen.
• Acute (in the past 30 days) or chronic enteric infections, including C. difficile.
• Chronic gastrointestinal disorder including inflammatory bowel disease, celiac disease , irritable bowel syndrome, chronic constipation or diarrhea
• Active neuropsychiatric disorder that requires anti-psychotic ie typical and atypical antipsychotics as well as anti-epileptics, levodopa, rivastigmine or any other neuropsychiatric medication with dopaminergic and cholinergic effects.
• Myocardial infarction or cerebrovascular accident in the six months prior to participation
• Coagulation disorders
• Chronic immunosuppressive medication (systemic) usage
• Anti-coagulation and anti-platelet agents such as plavix, warfarin, heparin, direct oral anticoagulants.
• Prior episode of C. difficile infection.
• Prosthetic heart valves or any other conditions that require pre-procedure antibiotics.
• Currently receiving chemotherapy
• Any medical, psychological or social condition, in the opinion of the investigator, would jeopardize the health or well-being of the participant, interfere with their participation in the study, or confound the results of the study.

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

Rockefeller University

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Enterocolitis, Pseudomembranous

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Technical problems with the methodology to identify neurons in the tissue samples using histological analysis delayed further analysis of the remaining samples until a better method can be worked out. The methods for assessing glia were successful. Since neuronal and glial assessments are carried out at the same time on the same sample, further analysis is delayed until the methodologic issue is resolved.

Results Point of Contact

• Title: Clinical Research Officer
• Organization: The Rockefeller University Center for Clinical and Translational

kostr@rockefeller.edu

2123278408

Study Officials

• Begum Aydin, PhD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

• Yelina Alvarez, MD/PhD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: April 14, 2023
• First Posted: April 28, 2023
• Study Start: June 23, 2023
• Primary Completion: November 9, 2023
• Study Completion: November 9, 2023
• Last Updated: March 12, 2026
• Results First Posted: March 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)