search
Back to results

Azithromycin for Meibomian Gland Disease

Primary Purpose

Dry Eye, Neuropathic Eye Pain, Ocular Microbiome

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Azithromycin Oral Product
Placebo Oral
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Azithromycin

Arm Description

Outcomes

Primary Outcome Measures

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

Ocular surface microbiome testing
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).
Ocular surface microbiome testing
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).
Dry Eye Questionnaire 5 (DE-5)
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.
Dry Eye Questionnaire 5 (DE-5)
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.
Neuropathic Pain Inventory for the Eye (NPSI-E)
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Neuropathic Pain Inventory for the Eye (NPSI-E)
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Personal Health Questionnaire (PHQ-9)
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.
Personal Health Questionnaire (PHQ-9)
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.

Full Information

First Posted
June 27, 2018
Last Updated
January 29, 2021
Sponsor
University of California, San Francisco
search

1. Study Identification

Unique Protocol Identification Number
NCT03953118
Brief Title
Azithromycin for Meibomian Gland Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye, Neuropathic Eye Pain, Ocular Microbiome, Depression, Anxiety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Azithromycin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Azithromycin Oral Product
Other Intervention Name(s)
Zithromax
Intervention Description
Oral azithromycin dosed at 1 gram per week for 3 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo Oral
Intervention Description
Oral placebo tablet
Primary Outcome Measure Information:
Title
Ocular Surface Disease Index (OSDI) Questionnaire
Description
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.
Time Frame
Baseline to 1 month.
Title
Ocular Surface Disease Index (OSDI) Questionnaire
Description
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.
Time Frame
Baseline to 3 months.
Secondary Outcome Measure Information:
Title
Ocular surface microbiome testing
Description
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).
Time Frame
Baseline to 1 month.
Title
Ocular surface microbiome testing
Description
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).
Time Frame
Baseline to 3 months.
Title
Dry Eye Questionnaire 5 (DE-5)
Description
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.
Time Frame
Baseline to 1 month.
Title
Dry Eye Questionnaire 5 (DE-5)
Description
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.
Time Frame
Baseline to 3 months.
Title
Neuropathic Pain Inventory for the Eye (NPSI-E)
Description
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Time Frame
Baseline to 1 month.
Title
Neuropathic Pain Inventory for the Eye (NPSI-E)
Description
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Time Frame
Baseline to 3 months.
Title
Personal Health Questionnaire (PHQ-9)
Description
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.
Time Frame
Baseline to 1 month.
Title
Personal Health Questionnaire (PHQ-9)
Description
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.
Time Frame
Baseline to 3 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Khashayar Nattagh, BA
Phone
19499107667
Email
khash.nattagh@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Schallhorn, MD, MS
Email
julie.schallhorn@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Schallhorn, MD, MS
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thuy Doan, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
khashayar nattagh
Phone
949-910-7667
Email
knattagh@gmail.com
First Name & Middle Initial & Last Name & Degree
John A Gonzales, MD
First Name & Middle Initial & Last Name & Degree
Jennifer Rose-Nussbaumer, MD
First Name & Middle Initial & Last Name & Degree
Geremi Seitzman, MD
First Name & Middle Initial & Last Name & Degree
Neeti Parikh, MD
First Name & Middle Initial & Last Name & Degree
Matilda Chan, MD, PhD
First Name & Middle Initial & Last Name & Degree
Khashayar Nattagh, BA

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
18452369
Citation
Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care. 2008 Apr;14(3 Suppl):S102-6.
Results Reference
background
PubMed Identifier
17508117
Citation
The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107. doi: 10.1016/s1542-0124(12)70082-4.
Results Reference
background
PubMed Identifier
21450917
Citation
Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. doi: 10.1167/iovs.10-6997e. Print 2011 Mar. No abstract available.
Results Reference
background
PubMed Identifier
17075643
Citation
Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf. 2003 Jul;1(3):107-26. doi: 10.1016/s1542-0124(12)70139-8.
Results Reference
background
PubMed Identifier
21450915
Citation
Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1938-78. doi: 10.1167/iovs.10-6997c. Print 2011 Mar. No abstract available.
Results Reference
background
PubMed Identifier
24112227
Citation
King-Smith PE, Bailey MD, Braun RJ. Four characteristics and a model of an effective tear film lipid layer (TFLL). Ocul Surf. 2013 Oct;11(4):236-45. doi: 10.1016/j.jtos.2013.05.003. Epub 2013 Jul 12.
Results Reference
background
PubMed Identifier
22222996
Citation
Lane SS, DuBiner HB, Epstein RJ, Ernest PH, Greiner JV, Hardten DR, Holland EJ, Lemp MA, McDonald JE 2nd, Silbert DI, Blackie CA, Stevens CA, Bedi R. A new system, the LipiFlow, for the treatment of meibomian gland dysfunction. Cornea. 2012 Apr;31(4):396-404. doi: 10.1097/ICO.0b013e318239aaea.
Results Reference
background
PubMed Identifier
25128594
Citation
Lee H, Chung B, Kim KS, Seo KY, Choi BJ, Kim TI. Effects of topical loteprednol etabonate on tear cytokines and clinical outcomes in moderate and severe meibomian gland dysfunction: randomized clinical trial. Am J Ophthalmol. 2014 Dec;158(6):1172-1183.e1. doi: 10.1016/j.ajo.2014.08.015. Epub 2014 Aug 13.
Results Reference
background
PubMed Identifier
23135530
Citation
Prabhasawat P, Tesavibul N, Mahawong W. A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction. Cornea. 2012 Dec;31(12):1386-93. doi: 10.1097/ICO.0b013e31823cc098.
Results Reference
background
PubMed Identifier
19277245
Citation
Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336-56.
Results Reference
background
PubMed Identifier
27817918
Citation
Deinema LA, Vingrys AJ, Wong CY, Jackson DC, Chinnery HR, Downie LE. A Randomized, Double-Masked, Placebo-Controlled Clinical Trial of Two Forms of Omega-3 Supplements for Treating Dry Eye Disease. Ophthalmology. 2017 Jan;124(1):43-52. doi: 10.1016/j.ophtha.2016.09.023. Epub 2016 Nov 3.
Results Reference
background
PubMed Identifier
27570444
Citation
Hosseini K, Lindstrom RL, Foulks G, Nichols KK. A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin-0.1% dexamethasone combination compared to 1% azithromycin alone, 0.1% dexamethasone alone, and vehicle in the treatment of subjects with blepharitis. Clin Ophthalmol. 2016 Aug 10;10:1495-503. doi: 10.2147/OPTH.S110739. eCollection 2016.
Results Reference
background
PubMed Identifier
24201556
Citation
Greene JB, Jeng BH, Fintelmann RE, Margolis TP. Oral azithromycin for the treatment of meibomitis. JAMA Ophthalmol. 2014 Jan;132(1):121-2. doi: 10.1001/jamaophthalmol.2013.5295. No abstract available.
Results Reference
background
PubMed Identifier
16491814
Citation
Yoo SE, Lee DC, Chang MH. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol. 2005 Dec;19(4):258-63. doi: 10.3341/kjo.2005.19.4.258.
Results Reference
background
PubMed Identifier
12883348
Citation
Ta CN, Shine WE, McCulley JP, Pandya A, Trattler W, Norbury JW. Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis. Cornea. 2003 Aug;22(6):545-8. doi: 10.1097/00003226-200308000-00011.
Results Reference
background
PubMed Identifier
26707417
Citation
Wladis EJ, Bradley EA, Bilyk JR, Yen MT, Mawn LA. Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology. Ophthalmology. 2016 Mar;123(3):492-6. doi: 10.1016/j.ophtha.2015.10.062. Epub 2015 Dec 23.
Results Reference
background
PubMed Identifier
27473509
Citation
Watters GA, Turnbull PR, Swift S, Petty A, Craig JP. Ocular surface microbiome in meibomian gland dysfunction. Clin Exp Ophthalmol. 2017 Mar;45(2):105-111. doi: 10.1111/ceo.12810. Epub 2016 Sep 7.
Results Reference
background
PubMed Identifier
17935949
Citation
Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents. 2008 Jan;31(1):12-20. doi: 10.1016/j.ijantimicag.2007.08.001. Epub 2007 Nov 1.
Results Reference
background
PubMed Identifier
25125598
Citation
Liu Y, Ding J. The combined effect of azithromycin and insulin-like growth factor-1 on cultured human meibomian gland epithelial cells. Invest Ophthalmol Vis Sci. 2014 Aug 14;55(9):5596-601. doi: 10.1167/iovs.14-14782.
Results Reference
background
PubMed Identifier
24357250
Citation
Liu Y, Kam WR, Ding J, Sullivan DA. Effect of azithromycin on lipid accumulation in immortalized human meibomian gland epithelial cells. JAMA Ophthalmol. 2014 Feb;132(2):226-8. doi: 10.1001/jamaophthalmol.2013.6030. No abstract available.
Results Reference
background
PubMed Identifier
21849891
Citation
Igami TZ, Holzchuh R, Osaki TH, Santo RM, Kara-Jose N, Hida RY. Oral azithromycin for treatment of posterior blepharitis. Cornea. 2011 Oct;30(10):1145-9. doi: 10.1097/ICO.0b013e318207fc42.
Results Reference
background
PubMed Identifier
20508503
Citation
Haque RM, Torkildsen GL, Brubaker K, Zink RC, Kowalski RP, Mah FS, Pflugfelder SC. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea. 2010 Aug;29(8):871-7. doi: 10.1097/ICO.0b013e3181ca38a0.
Results Reference
background
PubMed Identifier
20689782
Citation
Luchs J. Azithromycin in DuraSite for the treatment of blepharitis. Clin Ophthalmol. 2010 Jul 30;4:681-8. doi: 10.2147/opth.s6370.
Results Reference
background
PubMed Identifier
10815152
Citation
Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001/archopht.118.5.615.
Results Reference
background
PubMed Identifier
19034129
Citation
Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea. 2008 Dec;27(10):1142-7. doi: 10.1097/ICO.0b013e3181814cff.
Results Reference
background
PubMed Identifier
22249431
Citation
Meadows JF, Ramamoorthy P, Nichols JJ, Nichols KK. Development of the 4-3-2-1 meibum expressibility scale. Eye Contact Lens. 2012 Mar;38(2):86-92. doi: 10.1097/ICL.0b013e318242b494.
Results Reference
background

Learn more about this trial

Azithromycin for Meibomian Gland Disease

We'll reach out to this number within 24 hrs