Clinical trial NCT05287425: The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects
Official title: The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects, a Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasal and Pharyngeal Microbiome
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2022-03-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Ophthalmic topical antibiotics are commonly prescribed in clinical practice for several indications such as bacterial conjunctivitis, keratitis, blepharitis, dacryocystitis and also as prophylaxis. Aminoglycosides (i.e. gentamicin) and fluoroquinolones (i.e. ciprofloxacin) are among the most frequently used substance classes.

There is evidence that topical non-antibiotic eye drops might have an effect on the nasopharyngeal mucosal flora. This seems logical due to the anatomical connection through the nasolacrimal duct and the fact that up to 80% of topically administered drug diffuse into the systemic circulation through the highly vascularized nasopharyngeal mucosa. However, in the literature no data on the effect of antibiotic eye drops on the nasal or pharyngeal microbiome are currently available.

Recently, new, non-culture based techniques for assessment of the bacterial microbiome have been developed, so-called "next-generation sequencing" (NGS). NGS utilizes universal primers targeting the 16S rRNA gene, which is ubiquitous across most bacteria. With this technique, it is possible to gain information about a wide range of the bacterial microbiome and not only on pre-selected species.

In the present study, NGS will be used to investigate the effect of antibiotic eye drops on the nasal and pharyngeal microbiome. For this purpose, healthy subjects will be randomized to either receive eye drops containing gentamicin, ciprofloxacin or topical lubricants as control. As secondary outcome, prevalence of bacterial resistance genes, as well as signs and symptoms of ocular surface damage will be assessed.

The study will be carried out in 2 parts. Since both formulations of topical antibiotics contain benzalkonium chloride which also has a potential effect on the nasal and pharyngeal mucosal flora, it is unknown how much benzalkonium chloride would contribute to changes in the nasal microbiome after administration of topical antibiotics. To overcome this problem, first a pilot study in 20 subjects will be performed in which subjects will be randomized to receive either eye drops containing gentamicin, ciprofloxacin, preservative-containing topical lubricants or preservative-free topical lubricants. Based on the results of this pilot study, the control for the main part of the study will be chosen, depending on the effect on the bacterial microbiome. The results of the pilot study could also provide useful data to adjust the sample size for the main study part. In the main study, 60 subjects will be randomized to receive gentamicin, ciprofloxacin or lubricant eye drops. The same examinations as described above will be performed after 1 week treatment as well as 1 week and 3 months after treatment.


Eligibility criteria: Inclusion Criteria:

* Men and women aged between 18 and 45 years
* Normal ophthalmic findings
* Tear Break Up Time \>10 seconds
* Schirmer I Test \> 10mm/5min
* Ametropia ≤ 6 diopters
* No use of topical eye or nasal drops in the last 3 months

Exclusion Criteria:

* Regular use of medication, abuse of alcoholic beverages or drugs
* Participation in a clinical trial in the 3 weeks preceding the study
* Treatment in the previous 3 weeks with any drug (except intake of hormonal contraceptives)
* Treatment with topical or systemic antibiotics within 8 weeks before inclusion
* Symptoms of a clinically relevant illness in the 3 weeks before the first study day
* History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs
* Known hypersensitivity to any of the components of the IMP under investigation or other study medication
* Pregnant or breast-feeding women
* Women of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (i.e. oral contraceptives, intra-uterine device, contraceptive implant or condoms)

Primary outcomes:
measure: Nasal bacterial microbiome
timeFrame: change after 1 week treatment
Secondary outcomes:
measure: Pharyngeal bacterial microbiome
timeFrame: change after 1 week treatment
measure: Antibiotic resistance gene prevalence
timeFrame: change after 1 week treatment
measure: Minimum inhibitory concentrations for gentamicin and ciprofloxacin
timeFrame: change after 1 week treatment
measure: Tear film thickness
timeFrame: change after 1 week treatment
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Clinical Pharmacology, Medical University of Vienna
Study officials:
References: