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Lack of funding
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This study aims to elucidate the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Azithromycin | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin Oral Product | Drug | Oral azithromycin dosed at 1 gram per week for 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to 1 month |
| 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. | Baseline to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julie Schallhorn, MD, MS | University of California, San Francisco | Principal Investigator |
| Thuy Doan, MD, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | San Francisco | California | 94143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18452369 | Background | Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care. 2008 Apr;14(3 Suppl):S102-6. | |
| 17508117 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo Oral: Oral placebo tablet |
| FG001 | Azithromycin | Azithromycin Oral Product: Oral azithromycin dosed at 1 gram per week for 3 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo Oral: Oral placebo tablet |
| BG001 | Azithromycin | Azithromycin Oral Product: Oral azithromycin dosed at 1 gram per week for 3 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 1 month |
|
Adverse event data were not collected.
Study terminated due to due to lack of funding prior to data collection, adverse events were not monitored.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo Oral: Oral placebo tablet | 0 |
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Study terminated due to lack of funding prior to data collection for outcome measures and adverse events. There are no data to report.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julie Schallhorn, MD | University of California San Francisco CA | 415-514-1922 | julie.schallhorn@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 2, 2018 | Jul 15, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| D003863 | Depression |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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| Placebo Oral | Drug | Oral placebo tablet |
|
| Baseline to 1 month |
| 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). | Baseline to 3 months |
| 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. | Baseline to 1 month |
| 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. | Baseline to 3 months |
| Neuropathic Pain Inventory for the Eye (NPSI-E) | 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) | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. | Baseline to 3 months |
| 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. | Baseline to 1 month |
| 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. | Baseline to 3 months |
| 21450917 | Background | 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. |
| 17075643 | Background | 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. |
| 21450915 | Background | 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. |
| 24112227 | Background | 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. |
| 22222996 | Background | 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. |
| 25128594 | Background | 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. |
| 23135530 | Background | 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. |
| 19277245 | Background | 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. |
| 27817918 | Background | 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. |
| 27570444 | Background | 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. |
| 24201556 | Background | 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. |
| 16491814 | Background | 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. |
| 12883348 | Background | 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. |
| 26707417 | Background | 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. |
| 27473509 | Background | 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. |
| 17935949 | Background | 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. |
| 25125598 | Background | 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. |
| 24357250 | Background | 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. |
| 21849891 | Background | 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. |
| 20508503 | Background | 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. |
| 20689782 | Background | Luchs J. Azithromycin in DuraSite for the treatment of blepharitis. Clin Ophthalmol. 2010 Jul 30;4:681-8. doi: 10.2147/opth.s6370. |
| 10815152 | Background | 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. |
| 19034129 | Background | 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. |
| 22249431 | Background | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
| Primary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 3 months |
|
|
| Secondary | 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). | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 1 month |
|
|
| Secondary | 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). | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 3 months |
|
|
| Secondary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 1 month |
|
|
| Secondary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 3 months |
|
|
| Secondary | Neuropathic Pain Inventory for the Eye (NPSI-E) | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. | study terminated prior to any data analysis | Posted | Baseline to 1 month. |
|
|
| Secondary | Neuropathic Pain Inventory for the Eye (NPSI-E) | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 3 months |
|
|
| Secondary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 1 month |
|
|
| Secondary | 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. | Study terminated prior to data collection for outcomes. No data were collected for this outcome measure. | Posted | Baseline to 3 months |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Azithromycin | Azithromycin Oral Product: Oral azithromycin dosed at 1 gram per week for 3 weeks | 0 | 0 | 0 | 0 | 0 | 0 |
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| D001523 |
| Mental Disorders |
| Organic Chemicals |