Skin Cancer
Conditions
Brief summary
The primary objective of this study is to evaluate the effects of a novel sunscreen formulation by assessing the extent of ultraviolet radiation (UVR)-induced direct and indirect cellular and DNA damage to human skin, in the presence vs absence of the sunscreen, in a population of healthy adults with fair skin (Fitzpatrick Scale type I, II or III).
Detailed description
Skin cancer is the most commonly diagnosed malignancy in the USA and ultraviolet radiation (UVR) exposure is the major environmental risk factor for skin cancer development. Currently available sunscreens utilize UVR filters that, while absorbing UVR energy, have been shown to induce ROS, resulting in oxidative DNA damage after UVR exposure. Organic sunscreen actives have also been shown to penetrate into the skin, raising direct toxicity, as well as irritant and photoallergic concerns. Further systemic absorption may result in additional health risks such as endocrine disruption. Novel sunscreens that more safely prevent both direct and indirect DNA damage are needed. The study team have produced a bioadhesive nanoparticle (BNP) sunscreen designed to keep organic UVR filters from penetrating into the skin and have incorporated non-toxic natural products into this sunscreen to further safely boost UVR absorbing capacity and reduce oxidative, indirect DNA damage. This study will test the capacity of this sunscreen to prevent direct and indirect cellular and DNA damage in human skin exposed to UVR.
Interventions
DRUGSunscreen
The sunscreen contains bioadhesive nanoparticles (BNP) encapsulating avobenzone and octocrylene plus the non-toxic natural products diosmin, ferulic acid, cytisine and trans-resveratrol.
OTHERUV Light
UV light to the correct sites, and the Multiport 610 solar simulator used to deliver 1 MED UVR to the appropriate subsites.
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Laboratory technicians will be blinded to treatment of samples.
Intervention model description
Within subject design where participant serves as own control.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Women of child-bearing potential must have negative urine pregnancy test * In good general health as evidenced by medical history * Fair skinned with Fitzpatrick Scale skin types I, II or III using the following Skin Type and Sunburn and Tanning History (based on the first 30-45 minutes of sun exposure after a winter season of no sun exposure): * I always burns easily; never tans (sensitive) * II always burns easily; tans minimally (sensitive) * III burns moderately; tans gradually (light brown) (normal)
Exclusion criteria
* Individuals with active or a history of dermatological disorders-psoriasis, rosacea, eczema, vitiligo, lupus, dermatomyositis, etc * Individuals known to be subject to any abnormal responses to sunlight, such as phototoxic or photoallergic response. * Current use of medication (topical or systemic) that is known to produce abnormal sunlight responses. * History of skin cancer (such as basal cell carcinoma, squamous cell carcinoma, melanoma) * Family history of melanoma * Presence of sunburn, suntan, scars, active dermal lesions or uneven skin tone on the test site. * Skin type falling under the Fitzpatrick Scale skin types IV, V or VI using the following Skin Type and Sunburn and Tanning History (based on the first 30-45 minutes of sun exposure after a winter season of no sun exposure): * IV Burns minimally; always tans well (moderate brown) (normal) * V Rarely burns; tans profusely (dark brown) (insensitive) * Use of sunscreen within the last week on the test site area (such that UV filter penetration may confound results) * Febrile illness within 48 hours. * Women with a positive urine pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | 5 minutes after UVR exposure | Ultraviolet radiation (UVR) exposure are indicative of direct DNA damage. DNA will be prepared and assayed by ELISA for quantification of CPDs. CPDs measured in samples obtained immediately after UVR exposure are indicative of direct DNA damage. DNA from skin biopsies was used to quantify the level of DNA damage, represented by CPD levels detected by enzyme-linked immunosorbent assay (ELISA) |
| Detectable DNA Strand Breaks | 5 minutes after UVR exposure | Formalin fixed paraffin embedded skin stained with anti-gH2AX to identify keratinocytes with DNA strand breaks. Indirect, oxidative DNA damage may result in DNA strand breaks that can be visualized by microscopic analysis after staining for gH2AX, which builds up within cells with DNA strand break. |
| Number of DNA Strand Breaks | 4 hours after UVR exposure | Formalin fixed paraffin embedded skin stained with anti-gH2AX to identify keratinocytes with DNA strand breaks. Indirect, oxidative DNA damage may result in DNA strand breaks that can be visualized by microscopic analysis after staining for gH2AX, which builds up within cells with DNA strand break. |
| Cellular Damage | 5 minutes after UVR exposure | Formalin fixed paraffin embedded skin stained with anti-3-nitrotyrosine to identify cellular damage. ROS and high energy triplet state species can result in nitration of tyrosine residues of cellular proteins. This type of damage can be visualized by microscopic visualization of 3-nitrotyrosine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunscreen and no Suncreen (All Participants) All participants will have biopsies from a portion of skin with sunscreen applied and a portion of skin without sunscreen applied | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Excluded from analysis because processed biopsy sample was inadequate for analysis | 1 |
Baseline characteristics
| Characteristic | Sunscreen and no Suncreen (All Participants) | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 30 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 30 participants | — |
| Sex: Female, Male Female | 18 Participants | — |
| Sex: Female, Male Male | 12 Participants | — |
| Skin Type (Fitzpatrick) Fitzpatrick Type I | 1 Participants | — |
| Skin Type (Fitzpatrick) Fitzpatrick Type II | 20 Participants | — |
| Skin Type (Fitzpatrick) Fitzpatrick Type III | 7 Participants | — |
| Skin Type (Fitzpatrick) Fitzpatrick Type II/III | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Cellular Damage
Formalin fixed paraffin embedded skin stained with anti-3-nitrotyrosine to identify cellular damage. ROS and high energy triplet state species can result in nitration of tyrosine residues of cellular proteins. This type of damage can be visualized by microscopic visualization of 3-nitrotyrosine.
Time frame: 5 minutes after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 1 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
Primary
Cellular Damage
Formalin fixed paraffin embedded skin stained with anti-3-nitrotyrosine to identify cellular damage. ROS and high energy triplet state species can result in nitration of tyrosine residues of cellular proteins. This type of damage can be visualized by microscopic visualization of 3-nitrotyrosine.
Time frame: 4 hours after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 1 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Cellular Damage | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Cellular Damage | Sunscreen | 0 fluorescence units | Standard Error 0 |
Primary
Detectable DNA Strand Breaks
Formalin fixed paraffin embedded skin stained with anti-gH2AX to identify keratinocytes with DNA strand breaks. Indirect, oxidative DNA damage may result in DNA strand breaks that can be visualized by microscopic analysis after staining for gH2AX, which builds up within cells with DNA strand break.
Time frame: 5 minutes after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | Detectable DNA Strand Breaks | No sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 1 | Detectable DNA Strand Breaks | Sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Detectable DNA Strand Breaks | No sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Detectable DNA Strand Breaks | Sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Detectable DNA Strand Breaks | No sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Detectable DNA Strand Breaks | Sunscreen (normalized) | 0 fluorescence units | Standard Error 0 |
Primary
DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement
Ultraviolet radiation (UVR) exposure are indicative of direct DNA damage. DNA will be prepared and assayed by ELISA for quantification of CPDs. CPDs measured in samples obtained immediately after UVR exposure are indicative of direct DNA damage. DNA from skin biopsies was used to quantify the level of DNA damage, represented by CPD levels detected by enzyme-linked immunosorbent assay (ELISA)
Time frame: 5 minutes after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.48 Optical Density Units | Standard Error 0.15 |
| Sunscreen Formulation 1 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 1.14 Optical Density Units | Standard Error 0.26 |
| Sunscreen Formulation 2 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.18 Optical Density Units | Standard Error 0.14 |
| Sunscreen Formulation 2 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 0.33 Optical Density Units | Standard Error 0.07 |
| Sunscreen Formulation 3 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.64 Optical Density Units | Standard Error 0.09 |
| Sunscreen Formulation 3 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 1.24 Optical Density Units | Standard Error 0.19 |
p-value: 0.003t-test, 2 sided
Primary
DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement
Ultraviolet radiation (UVR) exposure are indicative of direct DNA damage. DNA will be prepared and assayed by ELISA for quantification of CPDs. CPDs measured in samples obtained immediately after UVR exposure are indicative of direct DNA damage. DNA from skin biopsies was used to quantify the level of DNA damage, represented by CPD levels detected by enzyme-linked immunosorbent assay (ELISA)
Time frame: 4 hours after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.41 Optical Density Units | Standard Error 0.21 |
| Sunscreen Formulation 1 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 1.03 Optical Density Units | Standard Error 0.26 |
| Sunscreen Formulation 2 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.07 Optical Density Units | Standard Error 0.14 |
| Sunscreen Formulation 2 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 0.24 Optical Density Units | Standard Error 0.05 |
| Sunscreen Formulation 3 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | No sunscreen | 2.42 Optical Density Units | Standard Error 0.08 |
| Sunscreen Formulation 3 | DNA Damage Level by Cyclobutane Pyrimidine Dimer (CPD) Measurement | Sunscreen | 0.92 Optical Density Units | Standard Error 0.23 |
Primary
Number of DNA Strand Breaks
Formalin fixed paraffin embedded skin stained with anti-gH2AX to identify keratinocytes with DNA strand breaks. Indirect, oxidative DNA damage may result in DNA strand breaks that can be visualized by microscopic analysis after staining for gH2AX, which builds up within cells with DNA strand break.
Time frame: 4 hours after UVR exposure
Population: Test Sites were delineated on the subjects upper inner arm, then either No sunscreen was applied, or the Test Sunscreen was applied 1 time at the FDA prescribed level (2 mg/cm2) and dried for 15 minutes before UVR exposure. The test sites were biopsied 5 minutes and 4 hours after UVR exposure. Two biopsies (one with sunscreen and one without) were taken per participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunscreen Formulation 1 | Number of DNA Strand Breaks | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 1 | Number of DNA Strand Breaks | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Number of DNA Strand Breaks | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 2 | Number of DNA Strand Breaks | Sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Number of DNA Strand Breaks | No sunscreen | 0 fluorescence units | Standard Error 0 |
| Sunscreen Formulation 3 | Number of DNA Strand Breaks | Sunscreen | 0 fluorescence units | Standard Error 0 |