Microbiome Analysis for Rosacea

Recruiting in Palo Alto (17 mi)

Overseen by Anna Chien

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Johns Hopkins University

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

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial examines how different antimicrobial treatments affect the skin and gut bacteria in people with moderate to severe rosacea. It aims to see if these treatments can help by changing the bacteria that live on the skin and in the gut.

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.

What data supports the effectiveness of the drug for treating rosacea?

Research shows that using doxycycline, an oral antibiotic, can reduce the severity of rosacea symptoms by altering the skin's bacterial makeup. Additionally, combining topical ivermectin with doxycycline may target different inflammation pathways, potentially improving treatment outcomes for rosacea. ^{1 2 3 4 5}

Is the treatment safe for humans?

The treatment using doxycycline and ivermectin for rosacea is generally safe, with most side effects being mild or moderate, such as diarrhea, nausea, and headache. In studies, only a small percentage of participants experienced these side effects. ^{1 2 6 7 8}

How is the drug combination of Doxycycline and Ivermectin unique for treating rosacea?

The combination of oral doxycycline and topical ivermectin is unique for treating rosacea because it targets different inflammatory pathways involved in the condition. Doxycycline works systemically to reduce inflammation, while ivermectin is applied directly to the skin to target inflammatory lesions, offering a complementary approach that may be more effective than using either treatment alone. ^{2 3 4 5 9}

Research Team

Anna Chien

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Doxycycline (Antibiotic)
• Ivermectin Topical (Antiparasitic)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

References

1. United States 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. [2013]

2. United States 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. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Characterization and Analysis of the Skin Microbiota in Rosacea: Impact of Systemic Antibiotics. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Microbiota of Demodex mites from rosacea patients and controls. [2022]

5. Sweden pubmed.ncbi.nlm.nih.gov

Effect on the Skin Microbiota of Oral Minocycline for Rosacea. [2023]

6. United States 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). [2013]

7. United States 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. [2015]

8. United States 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. [2014]

9. England 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. [2022]