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The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT05287425
Recruitment Status : Recruiting
First Posted : March 18, 2022
Last Update Posted : March 18, 2022
Sponsor:
Information provided by (Responsible Party):
Doreen Schmidl, Medical University of Vienna

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.


Condition or disease Intervention/treatment Phase
Nasal and Pharyngeal Microbiome Drug: Gentamicin Ophthalmic Drug: Ciprofloxacin Ophthalmic Drug: Povidone Ophthalmic Drug: Povidone and Benzalkonium Chloride Ophthalmic Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects, a Phase II Study
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

Arm Intervention/treatment
Experimental: Gentamicin eye drops
4 drops daily in both eyes for 7 ± 1 days
Drug: Gentamicin Ophthalmic
4 drops daily in both eyes for 7 ± 1 days

Experimental: Ciprofloxacin eye drops
4 drops daily in both eyes for 7 ± 1 days
Drug: Ciprofloxacin Ophthalmic
4 drops daily in both eyes for 7 ± 1 days

Active Comparator: Povidone eye drops unpreserved
4 drops daily in both eyes for 7 ± 1 days
Drug: Povidone Ophthalmic
4 drops daily in both eyes for 7 ± 1 days

Active Comparator: Povidone eye drops preserved
4 drops daily in both eyes for 7 ± 1 days
Drug: Povidone and Benzalkonium Chloride Ophthalmic
4 drops daily in both eyes for 7 ± 1 days




Primary Outcome Measures :
  1. Nasal bacterial microbiome [ Time Frame: change after 1 week treatment ]
    16S rRNA gene sequencing


Secondary Outcome Measures :
  1. Pharyngeal bacterial microbiome [ Time Frame: change after 1 week treatment ]
    16S rRNA gene sequencing

  2. Antibiotic resistance gene prevalence [ Time Frame: change after 1 week treatment ]
  3. Minimum inhibitory concentrations for gentamicin and ciprofloxacin [ Time Frame: change after 1 week treatment ]
  4. Tear film thickness [ Time Frame: change after 1 week treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05287425


Contacts
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Contact: Doreen Schmidl, MD, PhD +43 1 40400 ext 29810 doreen.schmidl@meduniwien.ac.at

Locations
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Austria
Department of Clinical Pharmacology, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Doreen Schmidl, MD, PhD    +43 1 40400 ext 29810    doreen.schmidl@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
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Responsible Party: Doreen Schmidl, Assoc. Prof. PD, MD, PhD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT05287425    
Other Study ID Numbers: OPHT-240518
First Posted: March 18, 2022    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ciprofloxacin
Gentamicins
Benzalkonium Compounds
Povidone
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Protein Synthesis Inhibitors
Plasma Substitutes
Blood Substitutes
Anti-Infective Agents, Local