Ocular Rosacea Biome Study

Antimicrobial Resistance Clinical Trial

— ORBS  

Official title:

ORBS: Ocular Rosacea Biome Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296837
• Other study ID #: 21-34725
• Status: Recruiting
• Phase: Phase 4
• Start date: June 22, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: University of California, San Francisco
• Contact: Victoria Cavallino, MSPH
• Phone: (415) 353-2800
• Email: victoria.cavallino[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ocular rosacea is an inflammatory disease of the eyelids and ocular surface. Like the facial disease, the ocular condition is chronic and recurrent. Sequelae of ocular rosacea vary from mild to severe. Ocular rosacea may cause chronic eye redness, blepharitis, recurrent chalazia, dry eye, corneal erosion, corneal vascularization, and corneal ulceration. Rosacea affecting the cornea can result in vision loss. Prescription eye drops and ointments can be used topically to control mild ocular rosacea. However, severe disease, or rosacea that is not well controlled with local treatments is treated systemically. The most commonly used systemic treatment for rosacea is the bacteriostatic antibiotic doxycycline. Rosacea treatment doses of doxycycline vary widely. Treatment-dose doxycycline for systemic infections is 100mg twice a day. However, as rosacea is considered an inflammatory disease, doxycycline is often dosed at what is termed, sub-microbial dose doxycycline (SDD). Initially introduced in the oral medicine literature, SDD are doses 40mg and lower because systemic administration at this dose does not appear to alter the oral mucosa flora or increase resistance rates when given long-term for periodontal disease. Whereas 100mg doxycycline, even when given short term, may increase the percentage of culturable nasopharyngeal flora that is resistant to doxycycline. The FDA does not categorize SDD an antibiotic, stating this dosing is expected to exhibit only anti-inflammatory activity.

Description:

Even though SDD is widely used for the treatment of rosacea, very little confirmatory data exists, to indicate if this dose alters any other systemic mucosa flora or increases antibiotic resistance rates. The classification of 40mg as "sub-microbial" has never been evaluated in patients diagnosed with ocular rosacea. Additionally, confirmation of a "sub-microbial" dose has not been investigated with more sophisticated genomics and resistance tools such as metagenomic deep sequencing (MDS). The goal of this proposal is to use MDS to determine whether SDD given to patients with ocular rosacea can be truly considered sub-microbial, or if a 40mg dose of doxycycline can in fact alter the microbiome of the conjunctiva and gut and increase resistance rates when prescribed for 8 weeks. The investigators plan to evaluate the effect of SDD on resistance and microbiome alteration through a randomized controlled masked trial. This is a randomized, controlled, masked trial comparing sub-microbial dose doxycycline, treatment dose Doxycycline, and placebo in the treatment of ocular rosacea. Participants will be recruited from the F.I. Proctor Foundation and the Ophthalmology clinics at the UCSF Wayne and Gladys Valley Center for Vision and consented for participation in an IRB-approved study protocol. Participants with a diagnosis of ocular rosacea (n=50) will be prospectively enrolled and randomized to one of three arms in a 2:2:1 fashion: Arm A will receive submicrobial dose doxycycline (40mg) administered as 20mg twice day for 8 weeks Arm B will receive 200mg of oral doxycycline administered as 100mg twice a day for 8 weeks Arm C will receive a placebo twice a day for 8 weeks

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: October 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have symptomatic ocular disease attributed to ocular rosacea as the primary diagnosis
• Ability to give informed consent
• Be aged 18 years old or older

Exclusion Criteria:

• Have an active ocular or systemic infection
• Have a known allergy or intolerance to tetracycline antibiotics
• Have had prior use of oral antibiotics within the last three months
• Pregnancy or the possibility of becoming pregnant within the 8-week study medication timeline.

Related Conditions & MeSH terms

• Antimicrobial Resistance
• Ocular Rosacea
• Rosacea

Intervention

Drug:
• Doxycycline 40 MG ( 20mg twice daily)
Submicrobial dose doxycycline (40mg) to be administered as 20mg twice daily
• Doxycycline 200 MG ( 100 mg twice daily)
200 mg dose doxycycline to be administered as 100mg twice daily
• Placebo
Placebo to be administered in tablet form twice daily

Locations

Country	Name	City	State
United States	University of California, San Farncisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (10)

Anon. Periostat [package insert]. Place of publication: Galderma; 2001

Del Rosso JQ, Brantman S, Baldwin H. Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily. Dermatol Ther. 2022 Jan;35(1):e15180. doi: 10.1111/dth.15180. Epub 2021 Dec 2. — View Citation

Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008 Jun;7(6):573-6. No abstract available. — View Citation

Nagler AR, Del Rosso J. The Use of Oral Antibiotics in the Management of Rosacea. J Drugs Dermatol. 2019 Jun 1;18(6):506. — View Citation

Preshaw PM, Novak MJ, Mellonig J, Magnusson I, Polson A, Giannobile WV, Rowland RW, Thomas J, Walker C, Dawson DR, Sharkey D, Bradshaw MH. Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease. J Periodontol. 2008 Mar;79(3):440-52. doi: 10.1902/jop.2008.070375. — View Citation

Schaller M, Almeida LM, Bewley A, Cribier B, Dlova NC, Kautz G, Mannis M, Oon HH, Rajagopalan M, Steinhoff M, Thiboutot D, Troielli P, Webster G, Wu Y, van Zuuren E, Tan J. Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017 Feb;176(2):465-471. doi: 10.1111/bjd.15173. Epub 2017 Feb 5. — View Citation

Schaller M, Kemeny L, Havlickova B, Jackson JM, Ambroziak M, Lynde C, Gooderham M, Remenyik E, Del Rosso J, Weglowska J, Chavda R, Kerrouche N, Dirschka T, Johnson S. A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea. J Am Acad Dermatol. 2020 Feb;82(2):336-343. doi: 10.1016/j.jaad.2019.05.063. Epub 2019 May 29. Erratum In: J Am Acad Dermatol. 2021 May;84(5):1506. — View Citation

Skidmore R, Kovach R, Walker C, Thomas J, Bradshaw M, Leyden J, Powala C, Ashley R. Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. Arch Dermatol. 2003 Apr;139(4):459-64. doi: 10.1001/archderm.139.4.459. — View Citation

Woo YR, Lee SH, Cho SH, Lee JD, Kim HS. Characterization and Analysis of the Skin Microbiota in Rosacea: Impact of Systemic Antibiotics. J Clin Med. 2020 Jan 9;9(1):185. doi: 10.3390/jcm9010185. — View Citation

Zhang M, Silverberg JI, Kaffenberger BH. Prescription patterns and costs of acne/rosacea medications in Medicare patients vary by prescriber specialty. J Am Acad Dermatol. 2017 Sep;77(3):448-455.e2. doi: 10.1016/j.jaad.2017.04.1127. Epub 2017 Jun 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Antimicrobial Resistance (AMR) genetic determinants	The frequency of AMR genetic determinants in rectal swab samples between arms will be compared, correcting for baseline	8 weeks
Secondary	Differences in Simpson's diversity of the microbiome of the conjunctiva and gut	Simpson's diversity is the probability that any two randomly chosen reads will be for different organisms (at the genus level). This will be expressed in terms of effective number.	4 weeks , 8 weeks, 3 - 6 months
Secondary	Ocular Surface Disease Index (OSDI) will be compared	Scores range from 0 to 100, with higher scores indicating greater symptom severity.; Standard 12-question created by the Outcomes Research Group at Allergan Inc will be used.	4 weeks , 8 weeks, 3 - 6 months
Secondary	Tear Breakup Time (TBUT) scores will be compared	Numbers representing how many seconds after a full blink a discontinuity in the tear film appears.; Obtained with the Oculus keratography topographer; This is a scale typically measured from 1-10, and the seconds correspond to the amount of time it takes for a tear film discontinuity to be observed. The lower the number the faster the tear break up and the worse the objective dry eye.	4 weeks , 8 weeks, 3 - 6 months