Healthy
Conditions
Brief summary
The study to be performed will allow visualization of skin micropores following microneedle treatment in healthy subjects in 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. 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.
Interventions
OTHERMicropatch (microneedle patch)
Each micropatch contains an array of 50 microneedles.
Sponsors
University of Iowa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects will be healthy men and women between 18 and 45 years of age.
Exclusion criteria
1. Unable to give consent 2. Severe general allergies requiring chronic treatment with steroid or antihistamines 3. Previous adverse reaction to microneedle insertion 4. History of keloids 5. Known allergy or adverse reaction to medical tape/adhesive, or aloe vera 6. Any inflammatory diseases of the skin (including but not limited to: psoriasis, atopic dermatitis, and blistering skin disorders) 7. Any disease associated with altered immune function (including but not limited to: rheumatoid arthritis, diabetes, lupus, HIV/AIDS) 8. Any subject taking medication that impairs the immune system (including but not limited to corticosteroids, TNF inhibitors, monoclonal antibodies, chemotherapy agents) 9. Any current malignancy or history of malignancy present at the treatment sites 10. 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) 11. Uncontrolled mental illness that would, in the opinion of the investigator, affect the subject's ability to understand or reliably participate in the study 12. 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. 13. Any subjects that are pregnant/nursing will be excluded from participation. 14. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Micropore Depth, Upper Arm | Post microneedle application (Day 0), approximately 5 minutes | 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. |
| Micropore Depth, Volar Forearm | Post microneedle application (Day 0), approximately 5 minutes | 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. |
| Micropore Depth, Palm | Post microneedle application (Day 0), approximately 5 minutes | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Trans-epidermal Water Loss, Upper Arm | Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes | 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. |
| Skin Color | Baseline (Day 0), <30 seconds | Lightness/darkness of the skin color is measured with a tristimulus colorimeter and reported in a unitless scale called the CIELAB color space (sometimes also called the L\*a\*b\* color space). In this study we measured the value called L\*. The L\* values can range from 0 (black) to 100 (white). Higher L\* values denote lighter skin, while lower L\* values denote darker skin. The L\* measurement is an objective measurement of skin color and there is no better or worse values of L\*. The L\* values are collected from the all 9 sites (3 each at upper arm, volar forearm, and palm) and the measurements are averaged together and reported as the mean. |
| Change in Trans-epidermal Water Loss, Volar Forearm | Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes | 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. |
| Change in Trans-epidermal Water Loss, Palm | Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Micropatch Application 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.
Micropatch (microneedle patch): Each micropatch contains an array of 50 microneedles. | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Micropatch Application |
|---|---|
| Age, Continuous | 26 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 49 |
| other Total, other adverse events | 3 / 49 |
| serious Total, serious adverse events | 0 / 49 |
Outcome results
Primary
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.
Time frame: Post microneedle application (Day 0), approximately 5 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Micropore Depth, Palm | 102.8 micrometer | Standard Deviation 21.2 |
Primary
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.
Time frame: Post microneedle application (Day 0), approximately 5 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Micropore Depth, Upper Arm | 72.4 micrometer | Standard Deviation 10.7 |
Primary
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.
Time frame: Post microneedle application (Day 0), approximately 5 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Micropore Depth, Volar Forearm | 78.6 micrometer | Standard Deviation 12.6 |
Secondary
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.
Time frame: Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Change in Trans-epidermal Water Loss, Palm | 131.3 percentage change from baseline | Standard Deviation 46.1 |
Secondary
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.
Time frame: Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Change in Trans-epidermal Water Loss, Upper Arm | 267.4 percentage change from baseline | Standard Deviation 95.8 |
Secondary
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.
Time frame: Baseline (Day 0) and post-microneedle application (Day 0), approximately 1-3 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Change in Trans-epidermal Water Loss, Volar Forearm | 313.2 percentage change from baseline | Standard Deviation 112.3 |
Secondary
Skin Color
Lightness/darkness of the skin color is measured with a tristimulus colorimeter and reported in a unitless scale called the CIELAB color space (sometimes also called the L\*a\*b\* color space). In this study we measured the value called L\*. The L\* values can range from 0 (black) to 100 (white). Higher L\* values denote lighter skin, while lower L\* values denote darker skin. The L\* measurement is an objective measurement of skin color and there is no better or worse values of L\*. The L\* values are collected from the all 9 sites (3 each at upper arm, volar forearm, and palm) and the measurements are averaged together and reported as the mean.
Time frame: Baseline (Day 0), <30 seconds
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropatch Application | Skin Color | 58.9 L* (unitless measure on a scale) | Standard Deviation 8.6 |