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.
Is the drug Metronidazole a promising treatment for rosacea?Yes, Metronidazole is a promising treatment for rosacea. It has been used for over 30 years and is effective in treating moderate-to-severe rosacea and preventing relapses. The drug is well tolerated by most patients and comes in various formulations that are easy to use and gentle on the skin.7891012
What safety data is available for metronidazole treatment in rosacea?Metronidazole 1% gel has been evaluated for safety in terms of cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential. It was found to be non-irritating, with a low potential for sensitization and no evidence of phototoxic or photoallergic reactions. Compared to azelaic acid gel, metronidazole gel showed a lower potential for irritation. Clinical studies indicate that metronidazole is generally well tolerated with low toxicity, and adverse effects are mainly local reactions like burning and stinging.1391011
What data supports the idea that Metronidazole and Moisturizers for Rosacea is an effective treatment?The available research does not provide any data on Metronidazole and Moisturizers for Rosacea. Instead, it focuses on treatments for colorectal cancer, specifically comparing different chemotherapy drugs. Therefore, there is no information here to support the effectiveness of Metronidazole and Moisturizers for Rosacea.245613
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you must refrain from using any lotion, medication, or other topical product on your face for a set amount of time before the study.
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
I am over 18, not pregnant, and healthy.
Treatment Details
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.
4Treatment groups
Experimental Treatment
Group I: Metronidzole cream + Eucerin Healing Lotion moisturizerExperimental Treatment2 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 moisturizerExperimental Treatment2 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 moisturizerExperimental Treatment2 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 moisturizerExperimental Treatment2 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Duke University Medical CenterDurham, NC
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Who is running the clinical trial?
Duke UniversityLead Sponsor
National Rosacea SocietyCollaborator
References
Topical metronidazole: a new therapy for rosacea. [2013]The chemistry, mechanism of action, pharmacokinetics, and adverse effects of topically applied metronidazole are reviewed, and the drug's use and efficacy in the treatment of rosacea and other conditions are discussed. Metronidazole is a synthetic, nitroimidazole-derivative antibacterial and antiprotozoal agent. For topical use, metronidazole is available in the United States as an aqueous gel. Polar reduction products of the drug appear to be responsible for its antimicrobial effects, which include disruption of DNA. The mechanism by which metronidazole ameliorates the lesions and erythema of rosacea may be related to anti-inflammatory or immunosuppressive actions of the drug rather than to suppression of skin bacteria. Metronidazole does not seem to be appreciably absorbed after topical application to the skin. Little is known about the distribution and elimination of topically applied metronidazole. Topical metronidazole has been designated an orphan drug by the FDA for the treatment of rosacea. In clinical studies metronidazole 0.75% topical gel or 1% cream resulted in improvement in inflammatory lesions in 68-96% of patients. Like other currently available therapies, metronidazole is only palliative; when the drug is withdrawn, symptoms commonly recur. Topical metronidazole has been used with some success in the treatment of decubitus and other ulcers and in certain dental conditions. The drug seems to have low toxicity and generally is well tolerated when applied topically. The principal adverse effects are local reactions, such as burning and stinging. Topical metronidazole provides another option for the treatment of rosacea.
Overview of the tolerability of 'Tomudex' (raltitrexed): collective clinical experience in advanced colorectal cancer. [2019]The tolerability of raltitrexed ('Tomudex', formerly ZD1694) was examined during phase I, II and III clinical studies involving around 1000 patients with advanced colorectal cancer. The dose-limiting toxicities in the phase I studies were gastrointestinal toxicity, haematological suppression and asthenia. Adverse events during phase II and III studies were consistent with those seen during phase I. In all comparative studies, mucositis and leucopenia were markedly less frequent and less severe in patients treated with raltitrexed than with 5-fluorouracil + leucovorin.Thrombocytopenia was more common with raltitrexed but was not associated with an increase in clinically significant haemorrhage. Elevated transaminases were frequently reported with raltitrexed but were usually reversible with continued dosing and were not associated with clinical sequelae. Patients treated with 5-fluorouracil + leucovorin experienced greater toxicity during early treatment cycles than those treated with raltitrexed. Fewer dosage reductions due to toxicity and greater quality-of-life benefits were observed in these early treatment cycles in patients treated with raltitrexed. Moreover, the incidence of fatal adverse events in patients given the recommended dose of raltitrexed was similar between groups. Raltitrexed thus provides some tolerability advantages compared with 5-fluorouracil + leucovorin, mainly with respect to leucopenia and mucositis, and less overall toxicity in early treatment cycles. The toxicity profile of raltitrexed is that expected of an antimetabolite.
A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. [2013]The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low.
The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer. [2019]After many years, during which the assumption prevailed that adjuvant chemotherapy was of no benefit in patients with resectable adenocarcinoma of the colon, findings of several large USA studies published from the late 1980s have caused a marked shift in surgical and medical opinion. Although results in patients with Dukes' B disease have not shown any clear benefit, the efficacy of adjuvant chemotherapy has nevertheless been shown in those with Dukes' C colon cancer. As a result, the Mayo regimen of 5-fluorouracil (5-FU) with low-dose leucovorin (LV) has become accepted as standard adjuvant therapy in these patients. However, the disadvantages associated with standard 5-FU-based treatment, particularly those relating to its toxicity and inconvenience of administration, have generated interest in other regimens and agents. The novel direct and specific thymidylate synthase inhibitor raltitrexed ('Tomudex') has been associated with similar objective response rates to standard therapy with 5-FU plus LV in patients with advanced colorectal cancer. In addition, raltitrexed has an attractive tolerability profile compared with that of 5-FU plus LV (specifically with respect to lower incidences of mucositis and leucopenia), and the simple 3-weekly administration schedule may be considered more convenient by many patients and may reduce healthcare resource consumption. To investigate alternatives to the Mayo regimen in the adjuvant treatment of Dukes' C adenocarcinoma of the colon, two large European trials have been set up: (1) PETACC-1 (first Pan-European Trial for Adjuvant Treatment of Colon Cancer), to compare raltitrexed with the Mayo regimen of 5-FU and low-dose LV; (2) PETACC-2 (second Pan-European Trial), to compare the Mayo regimen with three regimens in which 5-FU is given by prolonged infusion. These trials will provide valuable international data to add to those from the USA and will assess the place of raltitrexed in the adjuvant treatment of Dukes' C colon cancer. They will also compare directly for the first time infusional and bolus 5-FU regimens in the adjuvant setting.
A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes. [2019]Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo (P
Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials. [2019]Raltitrexed (Tomudex), a thymidylate synthase inhibitor, is an alternative to 5-fluorouracil (5-FU)/leucovorin (LV) for the first-line treatment of advanced colorectal cancer. Following the completion of four phase III studies with raltitrexed at the recommended dose of 3.0 mg/m(2), it is opportune to review the efficacy and tolerability data of raltitrexed and suggest guidelines for appropriate patient management. Data are analysed from four phase III and five phase II studies including over 1300 patients with advanced colorectal cancer, some of whom were elderly or received higher doses of raltitrexed. Median survival with raltitrexed was comparable to that of bolus or infusional 5-FU/LV in three of the four randomised studies and objective response rates in the four trials were similar for the two agents. Response rates were at least comparable in elderly patients in phase II studies. For the majority of patients, treatment with raltitrexed was well tolerated even at doses higher than that recommended or in the elderly. As with other cytotoxic agents, serious and potentially life-threatening side-effects can occur; nevertheless, adherence to simple patient guidelines should minimise the incidence of serious side-effects with raltitrexed; these include the assessment of renal function before each and every treatment, dosage adjustment in the presence of renal impairment and close monitoring with prompt treatment of toxicities, particularly diarrhoea and neutropenia.
The role of topical metronidazole in the treatment of rosacea. [2014]Many topical and oral pharmacologic agents have shown well-tolerated efficacy for the treatment of rosacea. Metronidazole was the first topical therapy approved for rosacea and is still considered the foundation therapy by many researchers and dermatologists. The efficacy and tolerability of topical metronidazole in combination with an oral antibiotic or as monotherapy to maintain remissions have been shown in multiple well-controlled trials.
An update on the role of topical metronidazole in rosacea. [2013]Topical metronidazole (Noritate 1% Cream, Dermik; MetroCream 0.75% Cream, MetroLotion 0.75% Lotion, Metrogel 0.75% and 1% Topical Gel, Galderma) has been used for the treatment of rosacea for over 30 years. Several placebo-controlled trials have demonstrated its effectiveness in the treatment of moderate-to-severe rosacea. It is also effective in preventing relapses of disease and is well tolerated by most patients. A growing number of formulations are available.
A look at the safety of metronidazole 1% gel: cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential. [2013]Rosacea is a common, recurrent, inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The condition may cause serious psychologic morbidity and may significantly affect quality of life. The first topical rosacea therapy approved by the US Food and Drug Administration was metronidazole for the treatment of inflammatory lesions and erythema. Previously, metronidazole was available as a 0.75% gel. Improved solubility was achieved in a new, stable, aqueous gel that permitted the formulation of metronidazole 1.0%. This new formulation is highly spreadable, easy to use, cosmetically friendly, mild to the skin, nondrying, and moisturizing. The safety of metronidazole 1% gel was determined by the evaluation of its cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential in healthy male and female patients. In this formulation, metronidazole was not irritating under occlusive application. Additionally, metronidazole 1% gel had a low potential for causing sensitization reactions, and no evidence suggested phototoxic or photoallergic reactions.
A novel aqueous metronidazole 1% gel with hydrosolubilizing agents (HSA-3). [2013]Rosacea is a common chronic dermatosis that often is characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. Because the face is the predominant site of involvement, rosacea may cause serious psychologic trauma and can significantly affect the quality of life of individuals with the condition. The first topical therapy approved for rosacea by the US Food and Drug Administration was metronidazole for the treatment of inflammatory lesions and erythema. A stable aqueous gel formulation of 1% metronidazole has been developed with the novel combination of hydrosolubilizing agents. Metronidazole 1% gel is a clear gel that exhibits advantageous qualities. Some features of the new product include being highly spreadable, easy to use, cosmetically friendly, ultramild, nondrying, and moisturizing. Data are presented from a 21-day cumulative irritation study, an assessment of skin barrier function, an in vitro skin penetration study, an absorption following maximal topical exposure study, and a skin hydration study.
Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%. [2014]Topical therapy for rosacea aims to reduce inflammatory lesions and decrease erythema but can carry side effects such as stinging, pruritus, and burning. Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration-approved for the treatment of rosacea. The current study was conducted to assess the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study demonstrated a significantly greater poten tial for irritation from azelaic acid compared with metronidazole gel 0.75% (P
Innovative use of topical metronidazole. [2018]Metronidazole is a synthetic nitroimidazole derivative with antimicrobial and antiinflammatory properties. It was the first topical therapy approved solely for rosacea and remains a cornerstone of rosacea management. This article reviews the optimal use of topical metronidazole in the treatment of rosacea and other innovative but off-label dermatologic uses reported in the literature.
Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed. [2014]5-fluorouracil continues to be the cornerstone of treatment for colorectal cancer. Although fluoropyrimidines are generally considered as well-tolerated drugs, severe toxicities can be a major clinical problem, and the recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients. Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of administration.