Metronidazole and Moisturizers for Rosacea

Overseen By Jessica Oxendine, CMA III

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Allergies, Sun damage, Skin growths, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Topical metronidazole is a widely used first line treatment for erythemotelangiectatic and inflammatory rosacea. Commonly, a moisturizer is also used to restore the skin barrier and reduce inflammation. The purpose of this study is to assess the whether the common practice of applying moisturizer prior to topical metronidazole affects this medication's stratum corneum penetrance in rosacea patients. Participants will have one research office visit that will consist of having a randomly assigned combination of metronidazole and one of four moisturizers applied to their face, followed by non-invasive tape stripping of skin at the 1 hour and 4 hour time points. These tape strip samples will be analyzed with liquid chromatography mass spectrometry (LC-MS) for assessment of metronidazole penetrance in the stratum corneum in the presence of moisturizers. The target population will be rosacea patients in the age range of 18-60 years of age. This study has minimal risks/safety issues as topical metronidazole is an already FDA approved medication with an indication for rosacea and all investigated moisturizers are over-the-counter formulations commonly used within the rosacea patient population. Tape stripping will remove 5 levels of superficial stratum corneum, and will not result in bleeding, scarring, or other prolonged cosmetic disfigurement. Small, transient bruising may result from tape strip collection. The collected samples will have no to minimal biohazard risk, as the collected specimen for analysis will only contain skin scale; samples will be extracted with organic solvents and decontaminated with a 0.2 micron nylon filter prior to analysis on the LC-MS instrumentation.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using any type of lotion, medication, or other topical product on their face for a set amount of time before the study.

Is metronidazole safe for use in humans?

Metronidazole 1% gel is generally safe for use in humans, with studies showing it has low potential for irritation, sensitization (allergic reactions), and no evidence of phototoxic (light-induced skin damage) or photoallergic reactions. It is well tolerated when applied to the skin, with the main side effects being mild local reactions like burning and stinging. ^{1 2 3 4 5}

How is the drug metronidazole unique in treating rosacea?

Metronidazole is unique for rosacea treatment because it was the first topical therapy approved specifically for this condition, and it combines antimicrobial and anti-inflammatory properties. The newer 1% gel formulation is particularly notable for being easy to spread, cosmetically friendly, and moisturizing, which makes it gentle on the skin while effectively treating symptoms. ^{1 3 6 7 8}

Research Team

Matthew M Draelos, MD PhD

Principal Investigator

Duke University

John Murray, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for rosacea patients aged 18-60. Participants must be willing to have a combination of metronidazole and one of four moisturizers applied to their face, followed by non-invasive skin sampling at specific times during a single office visit.

Inclusion Criteria

Subjects willing to allow a series of tape pieces to be pressed and removed from their faces over a 4-hour period

Subjects in general good health as determined from a medical history

Subjects must read and sign the informed consent form after the nature of the study has been fully explained

Exclusion Criteria

Subjects with known allergies or sensitivities to ingredients contained in the test products

Subjects with an allergy to latex or adhesives

Subjects with excessive visible sun damage on the face, such that the dermatologist investigator considers the subject unsuitable for study entry

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a randomly assigned combination of metronidazole and one of four moisturizers applied to their face, followed by tape stripping at 1 hour and 4 hour time points

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects and the effectiveness of the treatment is assessed

1-2 weeks

Treatment Details

Interventions

• Metronidazole

Trial Overview The study tests if applying moisturizer before the topical rosacea medication metronidazole affects how well it penetrates the top layer of skin. It involves randomly pairing metronidazole with one of four different moisturizers and measuring drug levels in the skin after application.

Participant Groups

Group I: Metronidzole cream + Eucerin Healing Lotion moisturizer Experimental Treatment 2 Interventions

Apply Eucerin Healing Lotion (mineral oil (occlusive) and sorbitol/propylene glycol (humecants)) followed by metronidazole cream. Tape striping will occur at 1 hours and 4 hours post metronidazole application.

Group II: Metronidzole cream + CeraVe moisturizer Experimental Treatment 2 Interventions

Apply CeraVe (glycerin/hyaluronic acid (humectant), ceramides (intercellular lipid component), and dimethicone/petrolatum (occlusive)) moisturizer followed by metronidazole cream. Tape striping will occur at 1 hours and 4 hours post metronidazole application.

Group III: Metronidazole cream + Cetaphil moisturizer Experimental Treatment 2 Interventions

Apply Cetaphil (glycerin (humectant) and petrolatum (occlusive)) moisturizer followed by metronidazole cream. Tape striping will occur at 1 hours and 4 hours post metronidazole application.

Group IV: Metronidazole cream + Aveeno Calm and Restore Oat Gel moisturizer Experimental Treatment 2 Interventions

Apply Aveeno Calm and Restore Oat Gel (glycerin (humectant) and dimethicone (occlusive) and oat kernel flour based gel moisturizer) moisturizer followed by metronidazole cream. Tape striping will occur at 1 hours and 4 hours post metronidazole application.

Metronidazole is already approved in United States, European Union, India, Canada for the following indications:

Approved in United States as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in European Union as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in India as Metrogyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in Canada as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Rosacea Society

Collaborator

Trials

1

Recruited

20+

Findings from Research

The new 1.0% metronidazole gel formulation for treating rosacea is effective in reducing inflammatory lesions and erythema, and it is designed to be more user-friendly and cosmetically appealing than the previous 0.75% gel.

Safety evaluations showed that the 1% gel has low irritation potential, minimal risk of sensitization, and no evidence of phototoxic or photoallergic reactions, making it a safe option for patients with rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A look at the safety of metronidazole 1% gel: cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential. Beutner, KR., Lemke, S., Calvarese, B.[2013]

In a study involving 36 participants over 21 days, azelaic acid gel 15% was found to have a significantly higher potential for skin irritation compared to metronidazole gel 0.75%.

Metronidazole gel 0.75% also caused more irritation than metronidazole gel 1%, which had a similar irritation profile to white petrolatum, suggesting it may be a safer option for patients with rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%. Colón, LE., Johnson, LA., Gottschalk, RW.[2014]

A new 1% metronidazole gel formulation for treating rosacea has been developed, which is highly spreadable, easy to use, and moisturizing, making it cosmetically friendly for patients.

The gel has undergone various studies, including a 21-day irritation study and skin hydration assessments, demonstrating its safety and effectiveness for managing rosacea symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel aqueous metronidazole 1% gel with hydrosolubilizing agents (HSA-3). Dow, G., Basu, S.[2013]

In a ten-week clinical study involving a double-blind, randomized design, metronidazole 1 percent cream applied once daily significantly reduced rosacea lesions and improved skin redness compared to a vehicle cream.

The treatment was found to be safe, with a low incidence of skin-related adverse events, indicating it is a well-tolerated option for managing rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Breneman, DL., Stewart, D., Hevia, O., et al.[2013]

Topical metronidazole is effective in treating rosacea, with clinical studies showing improvement in inflammatory lesions for 68-96% of patients, primarily due to its anti-inflammatory properties rather than antibacterial effects.

The drug is well tolerated with low toxicity, though it can cause local reactions like burning and stinging; however, it is only a palliative treatment, as symptoms often return after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical metronidazole: a new therapy for rosacea. Schmadel, LK., McEvoy, GK.[2013]

Topical metronidazole has been effectively used for over 30 years to treat moderate-to-severe rosacea, supported by several placebo-controlled trials.

It not only helps in treating rosacea but also prevents relapses, and is generally well tolerated by patients, with multiple formulations available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the role of topical metronidazole in rosacea. Zip, C.[2013]

Metronidazole is an effective topical treatment for rosacea, recognized for its antimicrobial and anti-inflammatory properties, making it a key option in managing this skin condition.

The article also explores innovative off-label uses of metronidazole in dermatology, highlighting its versatility beyond just treating rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative use of topical metronidazole. Zip, CM.[2018]

Topical metronidazole is recognized as the foundational therapy for rosacea, demonstrating well-tolerated efficacy in both monotherapy and in combination with oral antibiotics.

Multiple well-controlled trials have confirmed that metronidazole effectively maintains remission in rosacea patients, highlighting its importance in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of topical metronidazole in the treatment of rosacea. Wolf, JE.[2014]

References

1. United States pubmed.ncbi.nlm.nih.gov

A look at the safety of metronidazole 1% gel: cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

A novel aqueous metronidazole 1% gel with hydrosolubilizing agents (HSA-3). [2013]

4. United States pubmed.ncbi.nlm.nih.gov

A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Topical metronidazole: a new therapy for rosacea. [2013]

6. Canada pubmed.ncbi.nlm.nih.gov

An update on the role of topical metronidazole in rosacea. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Innovative use of topical metronidazole. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

The role of topical metronidazole in the treatment of rosacea. [2014]