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Azithromycin for Meibomian Gland Disease

Sponsor
University of California, San Francisco (Other)
Overall Status
Recruiting
CT.gov ID
NCT03953118
Collaborator
(none)
40
Enrollment
1
Location
2
Arms
63
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Azithromycin Oral Product
  • Drug: Placebo Oral
 Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 1, 2018
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Ocular Surface Disease Index (OSDI) Questionnaire [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.

    2. Ocular Surface Disease Index (OSDI) Questionnaire [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.

    Secondary Outcome Measures

    1. Ocular surface microbiome testing [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).

    2. Ocular surface microbiome testing [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).

    3. Dry Eye Questionnaire 5 (DE-5) [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.

    4. Dry Eye Questionnaire 5 (DE-5) [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.

    5. Neuropathic Pain Inventory for the Eye (NPSI-E) [Baseline to 1 month.]

      Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.

    6. Neuropathic Pain Inventory for the Eye (NPSI-E) [Baseline to 3 months.]

      Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.

    7. Personal Health Questionnaire (PHQ-9) [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.

    8. Personal Health Questionnaire (PHQ-9) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco San Francisco California United States 94143

    Sponsors and Collaborators

    • University of California, San Francisco

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT03953118
    Other Study ID Numbers:
    • 17-23877
    First Posted:
    May 16, 2019
    Last Update Posted:
    Feb 3, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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
    Additional relevant MeSH terms:
    Eye Pain
    Meibomian Gland Dysfunction
    Azithromycin

    Study Results

    No Results Posted as of Feb 3, 2021