Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06434519
Status:
RECRUITING
Last Update Posted:
2024-05-30
First Post:
2024-05-16
Brief Title:
Metronidazole SC Penetrance With Moisturizers
Sponsor:
Duke University
Organization:
Duke University
Study Overview
Official Title:
Evaluation of the Effect of Moisturizers on the Absorption of Metronidazole Into the Stratum Corneum of Rosacea Patients With Tape Stripping and Liquid Chromatography-mass Spectrometry
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 medications 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 riskssafety 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 02 micron nylon filter prior to analysis on the LC-MS instrumentation
Detailed Description:
Rosacea is a debilitating spectrum of disease causing both socially embarrassing erythema and disfiguring rhinophyma Treatment is challenging and life-long often requiring clinicians to trial multiple medications such as azelaic acid metronidazole or ivermectin to achieve disease control The skin of rosacea patients inherently has impaired skin barrier function resulting in inflammation and hypersensitivity to most therapeutics Thus many clinicians encourage patients to augment their topical medications with personal moisturizers to optimize the skin barrier However there is limited data to support that moisturizers do not affect drug epidermal penetrance and efficacy To the investigators knowledge only a single trial assessing the effect of moisturizers on skin penetrance of azelaic acid has been published in the English literature In the era of evidence-based medicine it is critical to provide either the scientific data to support or to refute this medical dogma The investigators proposal addresses this gap in the basic science literature and will provide data to evaluate a long and widely-held dermatologist recommendation for the treatment of rosacea The investigators anticipate that there may be preferred combinations of medication and moisturizers based upon the matched lipophilicities and other chemical properties of the occlusive agent and therapeutic drug Identification of such combinations may lead to improved outcomes for those struggling with treatment-resistant rosacea and lead to additional pharmaceutical advances in the treatment of rosacea
Drug formulation is critical to the successful treatment of dermatologic disease An active ingredient must diffuse through the stratum corneum SC to reach the dermis to achieve its therapeutic effect In addition to the intrinsic chemical properties of the active compound dictating the kinetics of the diffusion process chemists tweak a topical formulations vehicle emulsifiers and polymers to enhance drug SC penetrance and overcome the skins evolutionary role as a barrier to the outside world The combination of drug with additional topical moisturizers inherently changes the chemical environment that the active drug must diffuse through to reach the dermis Moisturizers and other topical cosmetics are well established to affect dermal drug and toxin absorption For example moisturizers have been demonstrated to enhance dermal penetrance of herbicide 24-dichlorophenoxacetic acid in murine models Similarly occlusive moisturizers are often applied over steroids to enhance their anti-inflammatory efficacy presumably through improved epidermal penetration Increased penetrance is a case-by-case scenario however and considerable attention is dedicated to topical formulation to appropriately modulate therapeutic drug penetrance of the SC during the drug design process
To the investigators knowledge the formulation and timing of moisturizer application on drug efficacy in rosacea is understudied An extensive literature review revealed only a single study addressing this important question for the special case of azelaic acid with an in vitro Franz cell diffusion assay using donated trunk skin biopsies In this study a 14C radiolabeled 15 azelaic acid gel was applied to epidermis before or after the application of Dove Lotion CeraVe Moisturizer Lotion and Cetaphil Moisturizing Lotion The penetrance of azelaic acid into the SC was then assessed up to 48 hours post-application using liquid scintillation spectrometry Azelaic acid SC penetration was not statistically different between the moisturizers or timing of application although trends towards decreased penetration was noted in 1 of 3 studied moisturizers There are several limitations to this study First azelaic acid occupies a unique chemical space among rosacea therapies Azelaic acids lipophilicity LogP an important chemical property affecting epidermal drug penetrance is 16 compared with 583 00 -03 and -07 for ivermectin metronidazole monocycline and doxycycline respectively suggesting that azelaic acid is between 14e2 times more lipophilic to 17e4 times less lipophilic than other therapies Thus azelaic acid is a poor standard with which to assess moisturizers impact on SC drug penetrance Second truncal skin was used to assess azelaic acid SC penetrance Consequently the studys clinical relevance is limited as rosacea exclusively affects the face where the skin is much thinner and transdermal absorption occurs more readily Finally although a tritium diffusion control was implemented to select skin samples with relatively intact barrier function a Franz cell diffusion assay inherently utilizes dead enzymatically inactive skin Thus the results of a Franz cell assay is not necessarily clinically relevant or reflective of physiologically active skin on patients Further work is necessary to determine whether moisturizers affects drug SC penetrance in rosacea patients
In prior work the investigators made method advances that overcome many of the limitations of the Franz cell assay as it relates to clinical relevance Specifically the investigators have established a track record of assessing drug penetrance of topically delivered medications eg tazarotene allantoin ketoconazole and betamethasone dipropionate in the SC using minimally invasive D-squame tape stripes of human subjects in combination with liquid chromatography mass spectrometry LC-MS In these studies the investigators are able to assess drug penetrance with physiologically relevant skin and on skin affected by the disease of interest Therefore the methods the investigators propose for assessing metronidazole SC penetrance in the presence of moisturizers is now established as an efficient and reliable method for quantitating drug in the SC in a minimally invasive and clinically relevant context
Drug formulation is critical to the successful treatment of dermatologic disease An active ingredient must diffuse through the stratum corneum SC to reach the dermis to achieve its therapeutic effect In addition to the intrinsic chemical properties of the active compound dictating the kinetics of the diffusion process chemists tweak a topical formulations vehicle emulsifiers and polymers to enhance drug SC penetrance and overcome the skins evolutionary role as a barrier to the outside world The combination of drug with additional topical moisturizers inherently changes the chemical environment that the active drug must diffuse through to reach the dermis Moisturizers and other topical cosmetics are well established to affect dermal drug and toxin absorption For example moisturizers have been demonstrated to enhance dermal penetrance of herbicide 24-dichlorophenoxacetic acid in murine models Similarly occlusive moisturizers are often applied over steroids to enhance their anti-inflammatory efficacy presumably through improved epidermal penetration Increased penetrance is a case-by-case scenario however and considerable attention is dedicated to topical formulation to appropriately modulate therapeutic drug penetrance of the SC during the drug design process
To the investigators knowledge the formulation and timing of moisturizer application on drug efficacy in rosacea is understudied An extensive literature review revealed only a single study addressing this important question for the special case of azelaic acid with an in vitro Franz cell diffusion assay using donated trunk skin biopsies In this study a 14C radiolabeled 15 azelaic acid gel was applied to epidermis before or after the application of Dove Lotion CeraVe Moisturizer Lotion and Cetaphil Moisturizing Lotion The penetrance of azelaic acid into the SC was then assessed up to 48 hours post-application using liquid scintillation spectrometry Azelaic acid SC penetration was not statistically different between the moisturizers or timing of application although trends towards decreased penetration was noted in 1 of 3 studied moisturizers There are several limitations to this study First azelaic acid occupies a unique chemical space among rosacea therapies Azelaic acids lipophilicity LogP an important chemical property affecting epidermal drug penetrance is 16 compared with 583 00 -03 and -07 for ivermectin metronidazole monocycline and doxycycline respectively suggesting that azelaic acid is between 14e2 times more lipophilic to 17e4 times less lipophilic than other therapies Thus azelaic acid is a poor standard with which to assess moisturizers impact on SC drug penetrance Second truncal skin was used to assess azelaic acid SC penetrance Consequently the studys clinical relevance is limited as rosacea exclusively affects the face where the skin is much thinner and transdermal absorption occurs more readily Finally although a tritium diffusion control was implemented to select skin samples with relatively intact barrier function a Franz cell diffusion assay inherently utilizes dead enzymatically inactive skin Thus the results of a Franz cell assay is not necessarily clinically relevant or reflective of physiologically active skin on patients Further work is necessary to determine whether moisturizers affects drug SC penetrance in rosacea patients
In prior work the investigators made method advances that overcome many of the limitations of the Franz cell assay as it relates to clinical relevance Specifically the investigators have established a track record of assessing drug penetrance of topically delivered medications eg tazarotene allantoin ketoconazole and betamethasone dipropionate in the SC using minimally invasive D-squame tape stripes of human subjects in combination with liquid chromatography mass spectrometry LC-MS In these studies the investigators are able to assess drug penetrance with physiologically relevant skin and on skin affected by the disease of interest Therefore the methods the investigators propose for assessing metronidazole SC penetrance in the presence of moisturizers is now established as an efficient and reliable method for quantitating drug in the SC in a minimally invasive and clinically relevant context
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None