Azithromycin for Meibomian Gland Disease

January 29, 2021 updated by: University of California, San Francisco

A Randomized, Controlled Trial to Evaluate the Role of Oral Azithromycin in the Treatment of Symptomatic Meibomian Gland Disease and Its Effect on the Ocular Surface Microbiome

This study aims to elucidate the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, placebo-controlled, double masked trial of the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction. Dry eye syndrome (DES) is a persistent feeling of ocular discomfort that encompasses dryness, irritation, foreign body sensation and burning. In the United States, it is the most common non-refractive cause of visits to eye care providers, and has been shown to have a significant impact on quality of life of patients who suffer from this condition. most common cause of DES is Meibomian gland disease (MGD). In the vast majority of cases, MGD is not binding, but rather causes persistant ocular discomfort.

Oral antibiotics, particularly the tetracyclines and macrolides, are frequently prescribed for the treatment of MGD. There is little good-quality evidence to support this practice. This study is designed to evaluate the effectiveness of oral azithromycin on patient-reported dry eye symptoms. Concomitantly, we will also study the composition of the ocular surface microbiome in MGD, and its response for oral antibiotics.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Contact:
        • Sub-Investigator:
          • John A Gonzales, MD
        • Sub-Investigator:
          • Jennifer Rose-Nussbaumer, MD
        • Sub-Investigator:
          • Geremi Seitzman, MD
        • Sub-Investigator:
          • Neeti Parikh, MD
        • Sub-Investigator:
          • Matilda Chan, MD, PhD
        • Sub-Investigator:
          • Khashayar Nattagh, BA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Symptomatic Meibomian gland disease, defined as patient-reported ocular surface symptoms such as dryness, grittiness, foreign body sensation, or eye fatigue in combination with clinically identifiable Meibomian gland disease with Grade 2 or greater involvement on the Meibomian Gland Grading Scale (Section XV, item 2).
  • OSDI Score greater than or equal to 20
  • Ability to give informed consent

Exclusion Criteria:

  • Age less than 18 years
  • Allergy or intolerance to oral azithromycin or topical dexamethasone
  • Allergy or intolerance to the preservatives used in topical ophthalmic 0.1% dexamethasone: sodium bisulfite, phenylethyl alcohol, benzalkonium chloride
  • History of prolonged QT interval, history of torsades des pointes, congenital long QT syndrome, bradyarrhythmias, heart failure
  • Patients currently taking medications that prolong the QT interval (Table 1)
  • Aqueous deficiency dry eye defined as Schirmer's strip testing without anesthesia with £ 5mm of tears on two separate tests.
  • Ocular surface inflammatory disease, including cicatrizing conjunctivitis, graft versus host disease, Stevens Johnson syndrome
  • Atopic disease with ocular involvement
  • Limbal stem cell deficiency
  • Oral or topical ophthalmic antibiotic use within the last 90 days
  • Oral prednisone use >5mg per day
  • Topical ophthalmic steroid use within the past 30 days
  • Topical ophthalmic anti-inflammatory (including non-steroidal anti-inflammatory medications, lifitegrast, or cyclosporine) use within the past 30 days
  • Patients who are currently pregnant, planning on becoming pregnant during the study period, or currently breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo Oral
Oral placebo tablet
Active Comparator: Azithromycin
Drug: Azithromycin Oral Product
Oral azithromycin dosed at 1 gram per week for 3 weeks
Other Names:
  • Zithromax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular Surface Disease Index (OSDI) Questionnaire
Time Frame: Baseline to 1 month.
Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye.
Baseline to 1 month.
Ocular Surface Disease Index (OSDI) Questionnaire
Time Frame: Baseline to 3 months.
Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye.
Baseline to 3 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular surface microbiome testing
Time Frame: Baseline to 1 month.

To evaluate the composition of the ocular surface microbiome using Shannon's diversity index. The alpha diversity (local species pool) of the population will be analyzed and compared pre-and post-treatment within and between the azithromycin and control groups. The difference between the bacterial microbiome in the azithromycin and placebo arm will be assessed using a PERMANOVA with an L2 norm distance measure.

Secondary analyses will include L1 and L0 norms, as well as a phylogenetic distance. In addition, we will assess whether bacterial alpha diversity is decreased in the antibiotic treated arm with the primary outcome being the Simpson's index (L2), with secondary analyses assessing Shannon's (L1) and Richness (L0).
Baseline to 1 month.
Ocular surface microbiome testing
Time Frame: Baseline to 3 months.

To evaluate the composition of the ocular surface microbiome using Shannon's diversity index. The alpha diversity (local species pool) of the population will be analyzed and compared pre-and post-treatment within and between the azithromycin and control groups. The difference between the bacterial microbiome in the azithromycin and placebo arm will be assessed using a PERMANOVA with an L2 norm distance measure.

Secondary analyses will include L1 and L0 norms, as well as a phylogenetic distance. In addition, we will assess whether bacterial alpha diversity is decreased in the antibiotic treated arm with the primary outcome being the Simpson's index (L2), with secondary analyses assessing Shannon's (L1) and Richness (L0).
Baseline to 3 months.
Dry Eye Questionnaire 5 (DE-5)
Time Frame: Baseline to 1 month.
Dry eye questionnaire 5 - used to evaluate the degree of dry eye symptoms. Scores range from 0-22. A score of 0 represents the minimum dry eye symptoms someone may have and a score of 22 represents the maximum dry eye symptoms someone may have.
Baseline to 1 month.
Dry Eye Questionnaire 5 (DE-5)
Time Frame: Baseline to 3 months.
Dry eye questionnaire 5 - used to evaluate the degree of dry eye symptoms. Scores range from 0-22. A score of 0 represents the minimum dry eye symptoms someone may have and a score of 22 represents the maximum dry eye symptoms someone may have.
Baseline to 3 months.
Neuropathic Pain Inventory for the Eye (NPSI-E)
Time Frame: Baseline to 1 month.
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Baseline to 1 month.
Neuropathic Pain Inventory for the Eye (NPSI-E)
Time Frame: Baseline to 3 months.
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Baseline to 3 months.
Personal Health Questionnaire (PHQ-9)
Time Frame: Baseline to 1 month.
Personal Health Questionnaire - a brief anxiety and depression questionnaire. Will be used in this study to evaluate the interaction between depression/anxiety and response to treatment.
Baseline to 1 month.
Personal Health Questionnaire (PHQ-9)
Time Frame: Baseline to 3 months.
Personal Health Questionnaire - a brief anxiety and depression questionnaire. Will be used in this study to evaluate the interaction between depression/anxiety and response to treatment.
Baseline to 3 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Julie Schallhorn, MD, MS, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2018

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

June 27, 2018

First Submitted That Met QC Criteria

May 15, 2019

First Posted (Actual)

May 16, 2019

Study Record Updates

Last Update Posted (Actual)

February 3, 2021

Last Update Submitted That Met QC Criteria

January 29, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-23877

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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