Racial/Ethnic Differences in Microneedle Response

Study Overview
=================
Brief Summary
-----------------
The study to be performed will define the rate of skin barrier recovery following microneedle treatment of the skin in healthy subjects of differing racial/ethnic backgrounds.

Detailed Description
-----------------
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. Microneedles are a minimally invasive means of allowing drug molecules to cross the skin by creating micron-sized channels (also called micropores) in the skin, thereby increasing its permeability. Microneedles have been safely used in hundreds of patients for administration of drugs and vaccines through the skin. Studies have demonstrated that microneedle treatment is relatively painless and well-tolerated by most patients. Following microneedle treatment, the skin must heal the micropores in order to restore barrier function. In young healthy individuals this process takes approximately 48 to 72 hours when the skin is covered by an occlusive patch. The timeframe for micropore closure is longer in elderly individuals (>65 years of age), taking several days longer to restore the skin barrier. As evidenced by the differences in micropore closure rate observed with advancing age, biological variation can have a significant effect on the skin's healing properties. There are almost no data available regarding how race and ethnicity affect skin response to microneedle insertion. It is crucial to better understand how the rates of micropore closure vary in different racial/ethnic populations because the potential for variability in drug delivery is high if the recovery timeframes are poorly understood. In this study we will measure hydration and color to characterize the epidermal properties of individuals of different self-identified race and ethnicity. Measurements of trans-epidermal water loss and electrical impedance will be used to evaluate the formation of micropores in the skin; the electrical impedance measurements will be used to calculate the rate of micropore closure. All of these skin characteristics can be measured using noninvasive methods that are quick and painless.

Official Title
-----------------
Evaluating Racial and Ethnic Differences in Micropore Closure Rates After Microneedle Application to the Skin

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Device: Microneedle patch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects will be healthy men and women between 18 - 50 years of age who identify as African American or Black, Asian, Hispanic or Latino, American Indian/Alaska Native, Native Hawaiian/Other Pacific Islander, Caucasian/White, bi-/multiracial. Exclusion Criteria: Unable to give consent Severe general allergies requiring chronic treatment with steroids or antihistamines Previous adverse reaction to microneedle insertion Known allergy or adverse reaction to medical tape, adhesive, or aloe vera Anyone with inflammatory diseases of the skin or diseases that alter immune function Anyone taking any medications that impair the immune system will be excluded (contraceptives, vitamins, and topical products on the face will be allowed) Anyone with current malignancy or history of malignancy present at the treatment site (upper arm) Anyone with any of the following present at the treatment site (upper arm): eczema or scaling, inflammation, erythema, edema, blisters Anyone with uncontrolled mental illness that would, in the opinion of the physician, affect their ability to understand or reliably participate in the study Anyone taking medications in the following therapeutic classes will be excluded: HMGCoA reductase inhibitors (statins), oral or topical steroids, oral antibiotics, topical antibiotics at the local treatment site, topical antihistamines at the local treatment site, beta-blockers, and systemic or topical NSAIDS/analgesics Anyone who is pregnant or nursing Anyone with 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
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Microneedle application<br>This is the only study arm, which all participants complete. Nine sites on the upper arm will be identified. Baseline measurements of transepidermal water loss, electrical resistance, hydration, and color will be made at each site. The 9 sites will be divided into clusters of 3 sites each. The first cluster will have small microneedle patches applied to at each site. This will only occur on the first study day. Transepidermal water loss and electrical resistance are re-measured immediately after microneedle application. The sites will be covered with a small patch secured with medical tape. The second cluster of sites will not receive microneedle application but will just be covered with patches. The last cluster of sites will not have microneedle application or patches. Electrical resistance will be re-measured at all sites for 4 days after microneedle application. Measurements from the 2nd and 3rd cluster of sites allow each subject to serve as their own control in data analysis. | Device: Microneedle patch<br>* Each patch contains 50 microneedles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Micropore Closure Time | The time required for the skin barrier to be restored after microneedle application will be determined using electrical resistance measurements. Differences in the skin electrical resistance will be determined through measurements made every day with skin electrodes attached to an impedance meter. These data for micropore closure are only collected from the microneedle sites. Using the data collected from all 5 days an average micropore closure time will be calculated, which can be compared between subsets of participants based on race/ethnicity. | Five days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Trans-epidermal Water Loss | Percent change from baseline trans-epidermal water loss will be calculated after microneedle application, and these data are only collected from the microneedle sites. Percent change is calculated as (trans-epidermal water loss after microneedle application/baseline trans-epidermal water loss) x 100. | 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 calculated as the mean of measurements from all 9 sites on the arm. | Baseline (Day 0) | 
| Hydration | Baseline skin hydration will be measured using a capacitance probe. The software calculates arbitrary unitless values. Values less than 30 are considered very dry while values over 40 are considered sufficiently moisturized. Data are calculated as the mean of measurements from all 9 sites on the arm. | Baseline (Day 0) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peer Reviewed Research