Visualizing Dermal Micropores With OCT

Study Overview
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Brief Summary
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The study to be performed will allow visualization of skin micropores following microneedle treatment in healthy subjects in differing racial/ethnic backgrounds.

Detailed Description
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Transdermal drug delivery (by way of patches that adhere to the skin and deliver drug in a time-dependent fashion) allows for systemic drug delivery through the skin, while avoiding many of the side effects and challenges associated with oral or intravenous drug delivery. One significant challenge limiting the number of drug compounds that can be transdermally delivered is the hydrophobic nature of the skin, which provides a highly efficient barrier against the absorption of drug molecules. Micropatches are small patches with tiny projections that are a minimally invasive way to allow drug molecules to cross the skin by creating micron-sized channels (also called micropores) in the skin, thereby increasing its permeability. Micropatches have been safely used in hundreds of patients for administration of drugs and vaccines through the skin. Studies have demonstrated that micropatch treatment is relatively painless and well-tolerated by most patients. Following micropatch treatment, the skin must heal the micropores. In young healthy individuals this process takes approximately 48 to 72 hours when the skin is covered by an occlusive patch. One of the factors that may also affect micropore healing time is the depth of the micropores in the skin immediately after micropatch treatment. There are almost no data available regarding how race and ethnicity affect the depth of micropores after micropatch application. It is important to study differences in micropore depth so investigators can better understand why rates of micropore closure vary in different racial/ethnic populations. Without this information the potential for variability in drug delivery is high. In this study the investigators will objectively measure skin color with a colorimeter to characterize the epidermal properties of individuals of different self-identified races and ethnicities. Measurements of trans-epidermal water loss will be used to evaluate formation of micropores in the skin; electrical impedance measurements will be used to estimate rates of micropore closure. The investigators will visualize the micropores created after micropatch treatment with the use of an optical coherence tomography instrument that will allow for calculation of epidermal thickness and micropore depth. All of these skin characteristics can be measured using noninvasive methods that are quick and painless.

Official Title
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Evaluating Racial and Ethnic Differences in Dermal Micropore Formation Using Optical Coherence Tomography

Conditions
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Healthy

Intervention / Treatment
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* Other: Micropatch (microneedle patch)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be healthy men and women between 18 and 45 years of age. Exclusion Criteria: Unable to give consent Severe general allergies requiring chronic treatment with steroid or antihistamines Previous adverse reaction to microneedle insertion History of keloids Known allergy or adverse reaction to medical tape/adhesive, or aloe vera Any inflammatory diseases of the skin (including but not limited to: psoriasis, atopic dermatitis, and blistering skin disorders) Any disease associated with altered immune function (including but not limited to: rheumatoid arthritis, diabetes, lupus, HIV/AIDS) Any subject taking medication that impairs the immune system (including but not limited to corticosteroids, TNF inhibitors, monoclonal antibodies, chemotherapy agents) Any current malignancy or history of malignancy present at the treatment sites Eczema or scaling present at any treatment site; any current inflammation or irritation present at the treatment sites (including but not limited to: rash, inflammation, erythema, edema, blisters) Uncontrolled mental illness that would, in the opinion of the investigator, affect the subject's ability to understand or reliably participate in the study Subjects taking medications in the following therapeutic classes will be excluded: HMGCoA reductase inhibitors (statins), oral or topical steroids (at the local treatment site), oral antibiotics, topical antibiotics at the local treatment site, topical antihistamines at the local treatment site, beta-blockers, and systemic or topical NSAIDS/analgesics. A subject who has recently used oral or topical steroids, antibiotics, antihistamines, or analgesics may be enrolled if more than 5 elimination half-lives of the drug have passed since the last dose (this is a typical parameter in pharmacokinetics, when it is assumed that  97% of drug in the systemic circulation is eliminated after 5 half-lives). The estimated elimination half-life for any specific drug will be obtained from standard pharmacy references such as Micromedex or other comparable drug information references. Any subjects that are pregnant/nursing will be excluded from participation. Subjects will also be excluded for any condition that would, in the opinion of the PI or physician, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Micropatch application<br>All participants will complete this arm. Three sites each on the upper arm, volar (inner) forearm, and palm will be identified. Baseline measurements of trans-epidermal water loss, electrical resistance, and color will be made at each site. Baseline optical coherence tomography (OCT) scans will be made at each site. Color will only be measured at baseline. One site at each location will undergo the following interventions: 1) micropatch application and an occlusive covering, 2) micropatch application, but remain uncovered, 3) occlusive covering, no micropatch application. Micropatch application will only occur on the first day and does not contain any drug substance. Trans-epidermal water loss and electrical resistance are re-measured after micropatch removal, along with an additional OCT scan. Electrical resistance and OCT scans will be repeated at all sites for 2 days. Measurements from the 2nd and 3rd sites allow each subject to serve as their own control in data analysis. | Other: Micropatch (microneedle patch)<br>* Each micropatch contains an array of 50 microneedles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Micropore depth, upper arm | The depth of the micropore created at the upper arm will be measured using OCT scans. These data are only collected from the micropatch sites. Data will be calculated as the mean of micropore depth measured at all micropatch sites. | Post microneedle application (Day 0) | 
| Micropore depth, volar forearm | The depth of the micropore created at the volar forearm will be measured using OCT scans. These data are only collected from the micropatch sites. Data will be calculated as the mean of micropore depth measured at all micropatch sites. | Post microneedle application (Day 0) | 
| Micropore depth, palm | The depth of the micropore created at the palm will be measured using OCT scans. These data are only collected from the micropatch sites. Data will be calculated as the mean of micropore depth measured at all micropatch sites. | Post microneedle application (Day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in trans-epidermal water loss, upper arm | The percent change in trans-epidermal water loss from baseline to post-micropatch application at the upper arm sites will be calculated. These data are only collected from the micropatch sites. Percent change is calculated as (trans-epidermal water loss after micropatch application/baseline trans-epidermal water loss) x 100. Data will be calculated as the mean of measurements from the micropatch sites at the upper arm. | Baseline (Day 0) and post-microneedle application (Day 0) | 
| Change in trans-epidermal water loss, volar forearm | The percent change in trans-epidermal water loss from baseline to post-micropatch application at the volar forearm sites will be calculated. These data are only collected from the micropatch sites. Percent change is calculated as (trans-epidermal water loss after micropatch application/baseline trans-epidermal water loss) x 100. Data will be calculated as the mean of measurements from the micropatch sites at the volar forearm. | Baseline (Day 0) and post-microneedle application (Day 0) | 
| Change in trans-epidermal water loss, palm | The percent change in trans-epidermal water loss from baseline to post-micropatch application at the palm sites will be calculated. These data are only collected from the micropatch sites. Percent change is calculated as (trans-epidermal water loss after micropatch application/baseline trans-epidermal water loss) x 100. Data will be calculated as the mean of measurements from the micropatch sites at the palm. | Baseline (Day 0) and post-microneedle application (Day 0) | 
| Skin color | Lightness/darkness of the skin is measured with a tristimulus colorimeter and reported in a unitless value called L*. Higher L* values denote lighter skin, while lower L* values denote darker skin. Data are collected as the mean of measurements from the all 9 sites (3 each at upper arm, volar forearm, and palm). | Baseline (Day 0) |