Microbiome Analysis for Rosacea

Overseen By Ruizhi Wang

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Antibiotics, Steroids, NSAIDs, Antacids

Disqualifiers: Chronic gastrointestinal disease, Diabetes, Cardiac disease, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore differences in skin and gut bacteria between individuals with moderate to severe rosacea and those without the condition. It will examine changes in these bacteria after treatments such as Doxycycline (an antibiotic) and topical Ivermectin (a skin-applied cream). Suitable participants are those diagnosed with moderate to severe rosacea who have not recently undergone facial treatments or surgeries. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants an opportunity to contribute to groundbreaking discoveries.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must not have used topical antibiotics, steroids, or other anti-inflammatory medications on your face for 4 weeks, and systemic antibiotics, steroids, or other immunosuppressive agents for 8 weeks before starting. Additionally, you should not have taken proton pump inhibitors, H2 receptor antagonists, laxatives, antidiarrheal medication, NSAIDs, or antacids within 2 weeks prior to enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that doxycycline is generally safe for treating rosacea. In various studies, patients using doxycycline for rosacea did not experience major safety issues. Some minor side effects, such as a cold and diarrhea, have been reported but are uncommon.

Ivermectin cream is also considered safe for rosacea. In clinical trials involving over 2,000 people, the cream was well-tolerated. Side effects were rare and usually mild.

Both treatments have FDA approval for rosacea, indicating they have been tested for safety. However, discussing possible side effects with a healthcare provider before starting any new treatment is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rosacea because they explore different dosages and delivery methods of existing medications, potentially leading to better outcomes. Unlike standard treatments, which often include topical metronidazole or oral antibiotics like tetracycline, this trial investigates varying doses of doxycycline, including 40mg, 50mg, 100mg, and 200mg per day, to find the most effective and tolerable option. Additionally, it evaluates the use of topical ivermectin, a medication typically used for parasitic infections, applied directly to the skin once daily. By examining these unique combinations and applications, researchers aim to uncover more effective and targeted treatment strategies for managing rosacea symptoms.

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

Research has shown that doxycycline helps treat rosacea by reducing inflammation. A large study with 826 patients found that 40 mg capsules of doxycycline are safe and effective for treating papulopustular rosacea, which includes red bumps and pus-filled spots. In this trial, participants may receive different dosages of doxycycline, including 40 mg, 50 mg, 100 mg, or 200 mg per day.

For ivermectin cream, another treatment option in this trial, several studies have shown it can clear or nearly clear rosacea in 40% to 80% of people with moderate to severe symptoms. Ivermectin cream often outperforms other treatments like azelaic acid and metronidazole.

Both treatments have been proven to reduce symptoms and improve skin conditions in people with rosacea. ^{1 6 7 8 9}

Who Is on the Research Team?

Anna Chien

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Adults over 18 with moderate-to-severe erythematotelangiectatic or papulopustular rosacea, or those without rosacea for control. Must understand the study and follow its rules. Can't join if they've had major GI surgery, bleeding disorders, recent facial treatments, certain drug use in past weeks, known allergies to trial medications, chronic diseases like diabetes or immunodeficiency, excessive scarring tendencies, are pregnant or have significant hair growth affecting evaluation.

Inclusion Criteria

I am over 18 years old.

I can understand and communicate with my doctor.

Participants must be willing and comply with the requirements of the protocol.

Exclusion Criteria

I am willing to not wash my face or wear makeup for 24 hours before the sampling visit.

I haven't used strong medications for skin issues recently.

I have a known bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying formulations of doxycycline or topical ivermectin for 28 days

4 weeks

1 visit (in-person) at baseline

Follow-up

Participants are monitored for changes in skin and gut microbiome after treatment

4 weeks

1 visit (in-person) at 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline
• Ivermectin Topical

Trial Overview

The trial is studying how two treatments—topical Ivermectin and oral Doxycycline—affect the skin and gut microbiome in people with rosacea compared to those without it. It uses DNA sequencing techniques to identify changes in microbial communities after treatment.

How Is the Trial Designed?

Group I: Topical ivermectin(1%) Experimental Treatment 1 Intervention

Topical ivermectin will be applied once a day for 28 days.

Group II: Doxycycline 50mg/day Experimental Treatment 1 Intervention

Doxycycline 50mg will be administered once a day per oral for 28 days.

Group III: Doxycycline 40mg/day Experimental Treatment 1 Intervention

Doxycycline 40mg will be administered once a day per oral for 28 days.

Group IV: Doxycycline 200mg/day Experimental Treatment 1 Intervention

Doxycycline 100mg will be administered twice a day per oral for 28 days.

Group V: Doxycycline 100mg/day Experimental Treatment 1 Intervention

Doxycycline 100mg will be administered once a day per oral for 28 days.

Group VI: Control Active Control 1 Intervention

No intervention will be performed.

Doxycycline is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in European Union as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Canada as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Japan as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Topical ivermectin cream and oral doxycycline are both effective treatments for papulopustular rosacea, targeting different inflammatory pathways, which suggests that using them together could enhance treatment outcomes.

The combination of these two therapies is proposed as a promising first-line approach for managing rosacea, as they complement each other's mechanisms of action to address the various signs and symptoms of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Ivermectin 10 mg/g and Oral Doxycycline 40 mg Modified-Release: Current Evidence on the Complementary Use of Anti-Inflammatory Rosacea Treatments. Steinhoff, M., Vocanson, M., Voegel, JJ., et al.[2018]

Oral minocycline treatment for 6 weeks in patients with rosacea led to significant improvements in skin condition, as indicated by changes in Investigator Global Assessment scores, and positively altered the skin microbiota by increasing α-diversity.

The treatment reduced harmful bacteria like Cutibacterium and Staphylococcus, while increasing beneficial metabolites such as butyrate, which may help reduce skin inflammation and support skin barrier repair; however, it also raised concerns about increased antibiotic resistance in the skin microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on the Skin Microbiota of Oral Minocycline for Rosacea. Zhang, Y., Zhou, Y., Humbert, P., et al.[2023]

In a study involving 40 patients, the combination of subantimicrobial doses of doxycycline (20 mg twice daily) with topical metronidazole significantly reduced inflammatory lesions in rosacea compared to metronidazole alone, with results observed as early as week 4.

The benefits of doxycycline were maintained even after transitioning to monotherapy, suggesting it could be an effective long-term maintenance treatment for rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. Sanchez, J., Somolinos, AL., Almodóvar, PI., et al.[2013]

In a 12-week phase 4 trial involving participants with papulopustular rosacea, once daily subantimicrobial-dose doxycycline (40 mg) significantly improved symptoms, with 75.7% of participants achieving clear or near clear IGA scores by the end of the study.

The treatment was well-tolerated, with only 7% of participants experiencing mild to moderate adverse events, indicating that doxycycline is a safe and effective option for individuals still symptomatic despite topical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) once daily as add-on therapy to existing topical regimens for the treatment of papulopustular rosacea: results from a community-based trial. Del Rosso, JQ.[2015]

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]

This randomized controlled trial aims to evaluate the effects of a sub-microbial dose (40 mg) of doxycycline compared to a standard antibiotic dose (200 mg) and a placebo on patients with ocular rosacea, focusing on antimicrobial resistance and changes in bacterial composition in the ocular and gut flora.

By using RNA sequencing and assessing both subjective and objective measures of ocular health, the study seeks to provide insights into the safety and efficacy of long-term sub-microbial antibiotic treatment for chronic ocular inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Mahmud, H., Keenan, JD., Gonzales, J., et al.[2022]

A study of 12 rosacea patients showed that oral doxycycline treatment for six weeks effectively reduced the severity of rosacea symptoms, indicating its efficacy as a treatment option.

The treatment altered the skin microbiota by increasing the abundance of Weissella confusa, but did not significantly change overall bacterial diversity, suggesting that while antibiotics can impact specific bacteria, they may not drastically shift the entire microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Analysis of the Skin Microbiota in Rosacea: Impact of Systemic Antibiotics. Woo, YR., Lee, SH., Cho, SH., et al.[2020]

A study analyzing the microbiota of Demodex mites from patients with different types of rosacea revealed a diverse range of 86 identified species, including 36 that are specific to Demodex.

In patients with papulopustular rosacea, there was a notable shift in the microbiota composition, with increased levels of Proteobacteria and Firmicutes and a decrease in Actinobacteria, suggesting a potential link between these microbial changes and the severity of rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota of Demodex mites from rosacea patients and controls. Murillo, N., Aubert, J., Raoult, D.[2022]

In a study of 207 participants with mild-to-moderate rosacea, both azelaic acid gel (15%) and metronidazole gel (1%) combined with doxycycline (40 mg daily) were found to be safe and effective treatments over a 12-week period.

The azelaic acid regimen showed a potential trend for greater and faster improvement in rosacea symptoms compared to the metronidazole regimen, suggesting it may be a more effective option for initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea. Del Rosso, JQ., Bruce, S., Jarratt, M., et al.[2014]

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The studies assessed the efficacy and safety of DFD-29 (20–40 mg) compared to doxycycline (40 mg) in rosacea treatment over 16 weeks.

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frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1169916/full

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jaad.org/article/S0190-9622(10)01117-5/fulltext

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A large study of 826 patients confirms the safety and effectiveness of doxycycline monohydrate 40 mg capsules for the treatment of papulopustular rosacea.

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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.

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Vibramycin Uses, Side Effects & Warnings

This medicine will not treat facial redness caused by rosacea. Some forms of doxycycline are used to prevent malaria, to treat anthrax, or to treat infections ...