Low-Dose Doxycycline for Ocular Rosacea

(ORBS Trial)

Overseen By Brianna K Colado

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Oral antibiotics

Disqualifiers: Active infection, Tetracycline allergy, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different doses of doxycycline, a common antibiotic, to evaluate its effectiveness in treating ocular rosacea, an eye condition causing symptoms like redness and irritation. Researchers aim to determine if a lower dose can manage the condition effectively without the side effects associated with higher doses. Participants will receive either a low dose, a high dose, or a placebo (a pill with no active medicine) for eight weeks, assigned randomly. The trial seeks individuals with noticeable symptoms of ocular rosacea as their primary eye issue. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used oral antibiotics in the last three months.

What is the safety track record for these treatments?

Research has shown that a low dose of 40 mg of doxycycline is generally safe for treating rosacea. Studies indicate that the most common side effects are mild, such as a sore throat and diarrhea, occurring in less than 2% of participants. The FDA notes that this low dose primarily reduces inflammation and typically does not cause antibiotic resistance.

Higher doses, like 200 mg (100 mg taken twice a day), carry more risks and are often used for bacterial infections. Common side effects at this level include an upset stomach and increased sensitivity to sunlight. Additionally, there is a greater risk of bacteria developing antibiotic resistance with this dose.

Both doses have been studied for rosacea, aiding individuals in making informed decisions. It is important to consult healthcare providers to determine the best option for individual health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the low-dose doxycycline treatment for ocular rosacea because it offers a gentler approach compared to higher doses traditionally used. Unlike standard treatments that often rely on higher doses of antibiotics, the 40mg submicrobial dose aims to reduce inflammation with minimal antibiotic exposure, potentially minimizing side effects and resistance. This treatment harnesses the anti-inflammatory properties of doxycycline while using a lower dose, which could maintain effectiveness while improving patient tolerance.

What evidence suggests that this trial's treatments could be effective for ocular rosacea?

Research has shown that doxycycline can help treat eye symptoms of rosacea. In this trial, participants will join different treatment arms. One arm will receive a 100 mg dose of doxycycline, which studies have found improves symptoms in up to 100% of patients. Although this dose is effective, it may increase the risk of antibiotic resistance. Another arm will receive a lower dose of 40 mg daily, which also helps, with 80% of patients noticing fewer symptoms. The 40 mg dose primarily reduces inflammation and avoids the antibiotic effects that can disrupt normal bacteria. Both doses are promising: the higher dose is very effective, while the lower dose offers benefits with fewer side effects. ^{1 5 6 7 8}

Who Is on the Research Team?

Gerami Seitzman, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with symptomatic ocular rosacea, which affects the eyes and eyelids. Participants must be able to consent and not have used oral antibiotics in the last three months. They can't join if they're allergic to tetracycline antibiotics, currently have an infection, or are pregnant or might become pregnant during the study.

Inclusion Criteria

My main health issue is eye problems due to rosacea.

Ability to give informed consent

Exclusion Criteria

You are allergic or intolerant to tetracycline antibiotics.

I have taken oral antibiotics in the last three months.

I currently have an eye or body-wide infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive submicrobial dose doxycycline, treatment dose doxycycline, or placebo for 8 weeks

8 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of ocular surface disease index and microbiome diversity

3-6 months

Follow-up visits at 4 weeks, 8 weeks, and 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline 100 MG Oral Tablet
• Doxycycline 200 MG ( 100 mg twice daily)
• Doxycycline 40 MG ( 20mg twice daily)
• Doxycycline 40 MG Oral Tablet
• Placebo

Trial Overview The study tests two doses of doxycycline (40mg daily as SDD and 200mg daily) against a placebo to see how well they control severe ocular rosacea symptoms like eye redness and corneal issues without causing antimicrobial resistance.

How Is the Trial Designed?

Group I: 40mg of oral doxycycline Experimental Treatment 1 Intervention

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

Group II: 100mg of oral doxycycline Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

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

Doxycycline 100 MG Oral Tablet is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Doxycycline for:

• Rosacea
• Acne
• Periodontal disease
• Chlamydia
• Lyme disease
• Rickettsial infections
• Anthrax

Approved in European Union as Doxycycline for:

• Rosacea
• Acne
• Periodontal disease
• Chlamydia
• Lyme disease
• Rickettsial infections
• Anthrax

Approved in Canada as Doxycycline for:

• Rosacea
• Acne
• Periodontal disease
• Chlamydia
• Lyme disease
• Rickettsial infections
• Anthrax

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In the ORCA trial involving 1197 participants, the 40-mg formulation of doxycycline significantly improved rosacea symptoms, with about 75% of participants achieving clear or near-clear skin by week 12.

The treatment was generally safe, with only 6.7% of participants reporting mild to moderate adverse events, such as diarrhea and nausea, indicating that doxycycline is a well-tolerated option for managing papulopustular rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, community-based, 12-week assessment of the effectiveness and safety of monotherapy with doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads). Webster, GF.[2013]

Anti-inflammatory dose doxycycline 40 mg capsules significantly improve rosacea symptoms compared to placebo, with a notable reduction in inflammatory lesions observed as early as 3 weeks into treatment, based on results from two large, randomized trials.

The 40 mg dose is effective without the higher concentrations needed for antibacterial effects, and it was well tolerated by patients, with most side effects being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline 40 mg capsules (30 mg immediate-release/10 mg delayed-release beads): anti-inflammatory dose in rosacea. McKeage, K., Deeks, ED.[2022]

Subantibiotic dose doxycycline (SDD40) is effective in treating inflammatory lesions of rosacea, showing consistent results across multiple randomized controlled trials (RCTs) involving 72 to 142 subjects, regardless of the patient's weight or severity of the condition.

The treatment was well tolerated with minimal gastrointestinal side effects, indicating a favorable safety profile for SDD40 in managing rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment of Inflammatory Lesions of Rosacea with Subantibiotic Dose Doxycycline Irrespective of Patient Weight or Baseline Lesion Count Severity. Del Rosso, JQ., York, JP., Bhatia, N.[2022]

In a study of 24 patients with ocular rosacea, doxycycline (100 mg/day) led to a 94% improvement in symptoms, with 12 patients becoming asymptomatic, while tetracycline hydrochloride (1g/day) resulted in 87% of patients being asymptomatic.

Both medications were effective in managing ocular rosacea symptoms, but gastrointestinal complications were noted in 13% of patients for both treatments, indicating a need for monitoring side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of doxycycline and tetracycline in ocular rosacea. Fruchtpery, J., Sagi, E.[2012]

Anti-inflammatory dose doxycycline (ADD) at 40 mg once daily is FDA-approved for treating rosacea and has shown effective anti-inflammatory activity without antibiotic effects, even with long-term use.

When used in combination with metronidazole gel, ADD leads to a faster therapeutic response in treating moderate to severe rosacea, while also having a better safety profile and lower gastrointestinal side effects compared to higher doses of doxycycline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflamatory dose doxycycline in the treatment of rosacea. Del Rosso, JQ.[2013]

Oracea, the first FDA-approved oral medication for rosacea, contains anti-inflammatory-dose doxycycline, which is not an antibiotic and does not contribute to antibiotic resistance, making it a safer long-term treatment option for the 13 million Americans affected by rosacea.

In clinical trials, Oracea has shown promising results for treating rosacea, and its once-daily dosing may improve patient compliance compared to other therapies, although it is contraindicated for certain populations, including pregnant women and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on rosacea and anti-inflammatory-dose doxycycline. Berman, B., Perez, OA., Zell, D.[2017]

A once-daily treatment of 40 mg slow-release doxycycline significantly improved symptoms of ocular rosacea in 15 patients, with severe complaints dropping from 73.3% to only 13.3% after 12 weeks of therapy.

The treatment was found to be safe, with only one patient experiencing a mild stomach ache, and long-term follow-up showed continued improvement in symptoms even after treatment was discontinued.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ocular rosacea with once-daily low-dose doxycycline. Sobolewska, B., Doycheva, D., Deuter, C., et al.[2022]

Doxycycline, used for treating rosacea, shows similar skin concentrations in both fed and fasting conditions after a 14-day treatment, indicating that food intake does not significantly affect its efficacy at steady state.

The study found that doxycycline accumulates more in the skin than in plasma, suggesting that its effectiveness in treating rosacea may be due to this significant dermal accumulation of the drug, regardless of food effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target site pharmacokinetics of doxycycline for rosacea in healthy volunteers is independent of the food effect. Pal, A., Matzneller, P., Gautam, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3047926/

Safety and efficacy of doxycycline in the treatment of rosacea Other prospective studies have demonstrated that between 87.5% and 100% of the patients have improvement of their symptoms of ocular rosacea after treatment ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/ddg.15290

Treatment of ocular rosacea: a systematic review Doxycycline, prescribed at 100 mg once or twice daily for 2 to 3 months has been reported as effective for management of ocular rosacea.

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06948-9

Ocular Rosacea microBiome Study (ORBS)—sub-microbial ... The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5076302/

Clinical Findings, Follow-up and Treatment Results in ... In a study including 15 ocular rosacea patients, slow-release doxycycline at a dose of 40 mg once daily resulted in a marked decrease in ocular complaints in 80 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002939414717507

Efficacy of Doxycycline and Tetracycline in Ocular Rosacea After six weeks of drug treatment, all patients except one had symptomatic improvement. Although most of the scores of the symptoms were significantly decreased ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/doxycycline-oral-route/description/drg-20068229

Doxycycline (oral route) - Side effects & dosage It is also used to treat pimples and abscesses (usually on the face) that are caused by rosacea, also known as acne rosacea or adult acne.

7. cdc.gov cdc.gov/sti/media/pdfs/2024/05/Doxycycline-Use-and-Adverse-Events.pdf

Doxycycline Use and Adverse Events MEDLINE/PubMed was searched for clinical studies that reported on adverse events with doxycycline use, speci cally focusing on side-e ects and metabolic.

8. drugs.com drugs.com/doxycycline.html

Doxycycline: Uses, Dosage, Side Effects, Warnings Doxycycline is used for bacterial infections, including acne, rosacea, urinary and respiratory tract infections, eye infections, gum disease, gonorrhea, ...