Healthy
Conditions
Keywords
Peer Reviewed Research
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.
Interventions
DEVICEMicroneedle patch
Each patch contains 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 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Micropore Closure Time | Five days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Trans-epidermal Water Loss | Baseline (Day 0) and post microneedle application (Day 0) | 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. |
| Skin Color | Baseline (Day 0) | 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. |
| Hydration | Baseline (Day 0) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment on this study was open from January 2018 to November 2019. Study procedures were conducted at the University of Iowa Hospitals and Clinics in the Clinical Research Clinic by members of the research staff.
Pre-assignment details
Subjects were screened after consenting to participate in the study. Participants that did not meet screening criteria were withdrawn from the study, 5 of our 132 consented participants fell into this exclusionary criteria. 9 of 132 participants signed the consent and stopped returning communication with study staff prior to scheduling their appointments, they were withdrawn from the study due to lack of follow-up. 5 of 132 voluntarily withdrew consent because of schedule conflicts.
Participants by arm
| Arm | Count |
|---|---|
| Microneedle Application This is the only arm of the study, which all participants complete. In each subject, 9 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 3 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, and the microneedle patches will then be discarded. 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 daily at all sites for 4 consecutive days after microneedle application. The measurements from the second and third cluster of sites allow each subject to serve as their own control in data analysis.
Microneedle patch: Each patch contains 50 microneedles. | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Microneedle Application |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 111 Participants |
| Age, Continuous | 25.9 Years STANDARD_DEVIATION 7.75 |
| Race/Ethnicity, Customized Asian | 32 Participants |
| Race/Ethnicity, Customized Bi-/Multi-racial | 10 Participants |
| Race/Ethnicity, Customized Black | 22 Participants |
| Race/Ethnicity, Customized Latino | 23 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants |
| Region of Enrollment United States | 111 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 113 |
| other Total, other adverse events | 1 / 113 |
| serious Total, serious adverse events | 0 / 113 |
Outcome results
Primary
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.
Time frame: Five days
Population: Data from all 111 participants was analyzed. The number in each row differs from the overall number because results are reported according to racial and ethnic subgroups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microneedle Application | Micropore Closure Time | Asian | 44.1 hours | Standard Deviation 14 |
| Microneedle Application | Micropore Closure Time | Bi-/Multi-racial | 48.0 hours | Standard Deviation 16 |
| Microneedle Application | Micropore Closure Time | Black | 66.5 hours | Standard Deviation 19.5 |
| Microneedle Application | Micropore Closure Time | White | 50.1 hours | Standard Deviation 12.4 |
| Microneedle Application | Micropore Closure Time | Latino | 61.1 hours | Standard Deviation 16.1 |
| Microneedle Application | Micropore Closure Time | Native American/Hawaiian | 72 hours | Standard Deviation 0 |
Secondary
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.
Time frame: Baseline (Day 0) and post microneedle application (Day 0)
Population: Data from all 111 participants was analyzed. The number in each row differs from the overall number because results are reported according to racial and ethnic subgroups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microneedle Application | Change in Trans-epidermal Water Loss | Asians | 212.81 Percantage change | Standard Deviation 58.83 |
| Microneedle Application | Change in Trans-epidermal Water Loss | Bi-/Multi-racial | 203.12 Percantage change | Standard Deviation 79.81 |
| Microneedle Application | Change in Trans-epidermal Water Loss | Black | 240.95 Percantage change | Standard Deviation 97.47 |
| Microneedle Application | Change in Trans-epidermal Water Loss | White | 228.25 Percantage change | Standard Deviation 75.58 |
| Microneedle Application | Change in Trans-epidermal Water Loss | Latino | 223.93 Percantage change | Standard Deviation 82.31 |
| Microneedle Application | Change in Trans-epidermal Water Loss | Native American/Hawaiian | 200 Percantage change | Standard Deviation 0 |
Secondary
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.
Time frame: Baseline (Day 0)
Population: Data from all 111 participants was analyzed. The number in each row differs from the overall number because results are reported according to racial and ethnic subgroups. Data are calculated as the mean of measurements from all 9 sites on the arm. Results are presented as prespecified in the protocol to collect and analyze data for all subjects together by ethnicity/race.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microneedle Application | Hydration | Asians | 38.32 Unitless | Standard Deviation 23.97 |
| Microneedle Application | Hydration | Bi-/Multi-racial | 50.27 Unitless | Standard Deviation 21.6 |
| Microneedle Application | Hydration | Black | 34.75 Unitless | Standard Deviation 18.49 |
| Microneedle Application | Hydration | White | 36.06 Unitless | Standard Deviation 18.81 |
| Microneedle Application | Hydration | Latino | 35.61 Unitless | Standard Deviation 14.23 |
| Microneedle Application | Hydration | Native American/Hawaiian | 24.1 Unitless | Standard Deviation 0 |
Secondary
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.
Time frame: Baseline (Day 0)
Population: Data from all 111 participants was analyzed. Data are calculated as the mean of measurements from all 9 sites on the arm. The number in each row differs from the overall number because results are reported according to racial and ethnic subgroups. Results are presented as prespecified in the protocol to collect and analyze data for all subjects together by ethnicity/race.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microneedle Application | Skin Color | Black | 40.61 Unitless | Standard Deviation 6.74 |
| Microneedle Application | Skin Color | Asian | 59.77 Unitless | Standard Deviation 7.62 |
| Microneedle Application | Skin Color | Bi-/Multi-racial | 61.12 Unitless | Standard Deviation 5.79 |
| Microneedle Application | Skin Color | White | 64.67 Unitless | Standard Deviation 4.71 |
| Microneedle Application | Skin Color | Latino | 58.84 Unitless | Standard Deviation 7.21 |
| Microneedle Application | Skin Color | Native American/Hawaiian | 60.37 Unitless | Standard Deviation 0 |