Ocular Rosacea Biome Study

NCT05296837 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 21-34725
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ocular Rosacea; Antimicrobial Resistance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Differences in Simpson's diversity of the microbiome of the conjunctiva and gut

  4 weeks , 8 weeks, 3 - 6 months

• Ocular Surface Disease Index (OSDI) will be compared

  4 weeks , 8 weeks, 3 - 6 months

• Tear Breakup Time (TBUT) scores will be compared

  4 weeks , 8 weeks, 3 - 6 months

Study Arms (3)

40mg of oral doxycycline

EXPERIMENTAL

Arm A will receive submicrobial dose doxycycline (40mg) administered as 20mg twice a day for 8 weeks

Drug: Doxycycline 40 MG ( 20mg twice daily)

100mg of oral doxycycline

ACTIVE COMPARATOR

Arm B will receive 200mg of oral doxycycline administered as 100mg twice a day for 8 weeks

Drug: Doxycycline 200 MG ( 100 mg twice daily)

Placebo

PLACEBO COMPARATOR

Arm C will receive a placebo twice a day for 8 weeks

Drug: Placebo

Interventions

Doxycycline 40 MG ( 20mg twice daily) DRUG

Submicrobial dose doxycycline (40mg) to be administered as 20mg twice daily

40mg of oral doxycycline

Doxycycline 200 MG ( 100 mg twice daily) DRUG

200 mg dose doxycycline to be administered as 100mg twice daily

100mg of oral doxycycline

Placebo DRUG

Placebo to be administered in tablet form twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Farncisco

San Francisco, California, 94143, United States

Location

Related Publications (11)

• 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.

  PMID: 31150711 BACKGROUND

• 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.

  PMID: 28651825 BACKGROUND

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

  PMID: 31251542 BACKGROUND

• 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.

  PMID: 18561589 BACKGROUND

• 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.

  PMID: 18315426 BACKGROUND

• 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.

  PMID: 12707093 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 27861741 BACKGROUND

• 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.

  PMID: 34713539 BACKGROUND

• 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.

  PMID: 31936625 BACKGROUND

• Mahmud H, Keenan JD, Gonzales J, Schallhorn J, Chan M, Arnold B, Cavallino V, Lietman TM, Doan T, Seitzman GD. Ocular Rosacea microBiome Study (ORBS)-sub-microbial versus antibiotic dosing of doxycycline versus placebo in treatment of symptomatic ocular rosacea: study protocol for a parallel-arm randomized clinical trial. Trials. 2022 Dec 20;23(1):1033. doi: 10.1186/s13063-022-06948-9.

  PMID: 36539810 DERIVED

MeSH Terms

Conditions

Rosacea

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Gerami Seitzman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All patients will be masked to their SDD allocation and informed that they will be taking a pill by mouth twice a day. Participants taking 40mg doxycycline will be taking one 20mg doxycycline pill twice a day. Participants taking 200mg doxycycline will be taking 100mg twice a day. Participants allocated to placebo will be taking a placebo pill twice daily All examining physicians responsible for TBUT determination and ocular photography will be masked to patient allocation assignment. The study analyst only will have access to the randomization key.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: March 16, 2022
• First Posted: March 25, 2022
• Study Start: June 22, 2023
• Primary Completion: July 11, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)