Metronidazole and Moisturizers for Rosacea

Overseen By Jessica Oxendine, CMA III

Age: 18+

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how moisturizers might affect the absorption of metronidazole cream, a treatment for rosacea, into the skin. Researchers aim to determine if applying a moisturizer before the medication influences its effectiveness in treating rosacea, a condition that causes redness and inflammation. During a single visit, participants will have metronidazole and one of four different moisturizers applied to their face, followed by gentle skin sampling to assess treatment penetration. This study may suit individuals with rosacea who are comfortable with temporary skin sampling and can remain calm during the trial. As an unphased trial, it offers a unique opportunity for individuals to contribute to understanding how moisturizers can enhance rosacea treatment.

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

Research has shown that metronidazole cream is generally safe for treating rosacea. The FDA has approved it for this use, confirming its safety through testing. In past studies, some users experienced mild skin reactions such as redness, itching, or dryness. These side effects are typically not serious and usually resolve over time.

The moisturizers tested with metronidazole are common over-the-counter products. People with rosacea often use them to soothe and protect their skin. These moisturizers are generally well-tolerated and do not present major safety concerns.

In this study, participants will have some tape strips applied to their skin, which might cause temporary bruising. However, this will not lead to any lasting skin issues. Overall, the treatments in this trial are considered safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different moisturizers can enhance the effectiveness of metronidazole cream for treating rosacea. Unlike the standard metronidazole treatment, this trial combines it with moisturizers like Aveeno, Cetaphil, CeraVe, and Eucerin, each having unique components like glycerin, hyaluronic acid, and ceramides that may improve skin barrier function. The trial aims to discover whether these combinations can provide faster relief or better results compared to using metronidazole alone, potentially offering a more effective and soothing treatment option for rosacea sufferers.

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

Research has shown that applying metronidazole gel to the skin effectively treats rosacea. In one study, 77% of participants using the gel experienced no symptoms after six months, compared to 58% who used a placebo. Another study found that metronidazole cream reduced redness by up to 26%. While azelaic acid may work better for some, metronidazole still helps many manage symptoms like redness and bumps. In this trial, participants will use metronidazole cream with different moisturizers, such as Aveeno Calm and Restore Oat Gel, Cetaphil, CeraVe, or Eucerin Healing Lotion, to maintain healthy skin and reduce inflammation. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew M Draelos, MD PhD

Principal Investigator

Duke University

John Murray, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11702300/

Topical metronidazole. A review of its use in rosacea In the only study, 77% of patients treated with metronidazole gel compared with 58% of placebo recipients (p < 0.05) remained in remission 6 months after the ...

2. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/189144

Topical Metronidazole Maintains Remissions of Rosacea Results In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11606923/

Once-daily topical metronidazole cream formulations in the ... The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0001731025002820

Efficacy of Widely Used Topical Drugs for Rosacea Azelaic acid has a better efficacy profile than metronidazole according to included studies. Minocycline proved effective improving the symptoms of rosacea.

5. cdn.mdedge.com cdn.mdedge.com/files/s3fs-public/Document/September-2017/079010073.pdf

The CLEAR Trial: Results of a Large Community-Based ... Although there is no evidence that medical therapies for rosacea, including topical metronida- zole, reduce the number of telangiectatic vessels, the use of a ...

6. vionausa.com vionausa.com/wp-content/uploads/2023/09/Metronidazole-Cream_SDS.pdf

Safety Data Sheet Metronidazole Topical Cream, Strength Metronidazole topical cream is contraindicated in individuals with a history of hypersensitivity to metronidazole, or other ingredients.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2003/020743s002lbl.pdf

C:\Data\My Documents\N20743S002AP - accessdata.fda.gov Clinical Studies: Safety and efficacy of NORITATE were evaluated in two randomized vehicle- controlled clinical studies for the treatment of rosacea, which ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/metronidazole-topical-route/description/drg-20064727

Metronidazole (topical route) - Side effects & dosage Metronidazole topical gel is used to treat inflammatory lesions (pimples and red bumps) caused by rosacea. Rosacea is a skin disease that causes redness and ...

9. healio.com healio.com/clinical-guidance/drugs/noritate

Noritate: Uses, Side Effects & Dosage For the treatment of rosacea, metronidazole is believed to work by decreasing swelling (inflammation). ... No safety and efficacy data established. Drug ...

10. webmd.com webmd.com/drugs/2/drug-75148/metronidazole-topical/details

Metronidazole topical - Uses, Side Effects, and More Topical metronidazole can cause skin reactions, including allergic reactions and contact dermatitis. Symptoms of a skin reaction can include ...