Aging
Conditions
Keywords
aging, ultraviolet exposure, skin fragility, sulforaphane
Brief summary
This study aims to compare the expression of keratins before and after application of sulforaphane (SF) to determine whether this agent alters skin fragility seen in both intrinsic and extrinsic skin aging and UV light exposure.
Detailed description
The primary purpose of the study is to compare the expression of keratins before and after application of sulforaphane (SF) and determine whether these findings alter skin fragility seen in both intrinsic and extrinsic skin aging as well as in ultraviolet (UV) light exposure. This investigation will be done in collaboration with researchers from the Department of Biochemistry and Molecular Biology and Bloomberg School of Public Health at Johns Hopkins University. The study population recruited by Johns Hopkins Department of Dermatology will include up to 50 individuals over the age of 18 with healthy skin. Each study participant will have four on-site study visits and will be asked to contribute photographs, undergo non invasive elasticity measurements, use topical sulforaphane for 7 days and contribute up to four biopsy specimens for laboratory study. The investigators will also evaluate any differences in keratins' expression in skin exposed to acute UV light, separately and after pretreatment with sulforaphane.
Interventions
DRUGSulforaphane
Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway.
RADIATIONNarrow-band Ultraviolet B exposure
The investigators will use a Lumera ultraviolet B (UVB) light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm).
PROCEDURE4 mm skin punch biopsy
All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Participants must be over the age of 18 years old with healthy skin; 2. Must be healthy enough to undergo skin biopsy, UV light irradiation, and other study procedures in the opinion of the investigator; 3. Must be willing to comply with the requirements of the protocol; 4. Must have the ability to understand and communicate with the investigator; 5. Participant must provide informed consent.
Exclusion criteria
1. Subjects who are unable to provide informed consent; 2. Subject with significant medical history or current skin diseases that the investigator feels is not safe for study participation; 3. Subjects who have been treated with systemic retinoids or steroids within the past month prior to entry to the study; 4. Subjects who have been treated with topical steroids, retinoids or other topical drugs used within 2 weeks prior to entry to the study; 5. Recently treated or current skin diseases that would affect clinical evaluation and biopsy; 6. Subjects with a known allergy to broccoli. 7. Presence or suspicion of bleeding disorder or diathesis which would complicate biopsy. 8. Subjects with a history of excessive scar or keloid formation in the past 10 years. 9. Pregnant or nursing subjects (self-reported). 10. Subjects with known allergy to anesthetics used. 11. Patients with history of investigational drug use in the 30 days prior to entry into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Change Score for Mottled Hyperpigmentation | Clinical Change Score for Mottled Hyperpigmentation , up to 1 week | Clinical assessment of mottled hyperpigmentation pre and post Sulforaphane (SF) treatment will be done for both photoprotected and photodamaged skin treated with sulforaphane. Mottled Hyperpigmentation Score system will be applied, with scale of 0 to 4, 4= clear improvement after 1 week of SF or placebo application. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gene Expression Changes as Assessed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) | Up to 6 months | We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using RT-PCR. |
| Gene Expression Changes as Assessed by Immunohistochemistry (IHC) | Up to 6 months | We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using IHC. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: No UV Exposure Two photoprotected sites will be identified. Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites.
4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin. | 9 |
| Group B With UV Exposure Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure.
Narrow-band Ultraviolet B exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm).
4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications | 0 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Group A: No UV Exposure |
|---|---|---|
| Age, Continuous | 57 years | 57 years |
| Race/Ethnicity, Customized Caucasian | 9 Participants | 9 Participants |
| Region of Enrollment United States | 9 Participants | 9 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 0 |
| other Total, other adverse events | 0 / 9 | 0 / 0 |
| serious Total, serious adverse events | 0 / 9 | 0 / 0 |
Outcome results
Primary
Clinical Change Score for Mottled Hyperpigmentation
Clinical assessment of mottled hyperpigmentation pre and post Sulforaphane (SF) treatment will be done for both photoprotected and photodamaged skin treated with sulforaphane. Mottled Hyperpigmentation Score system will be applied, with scale of 0 to 4, 4= clear improvement after 1 week of SF or placebo application.
Time frame: Clinical Change Score for Mottled Hyperpigmentation , up to 1 week
Population: We did not enroll any participant in group B. The results we got were not the comparison between no UV exposure group and UV exposure. Instead, the results were the clinical change score between the SF treated skin spots and no SF treated (placebo) skin spots of each participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: No UV Exposure - Sulforaphane | Clinical Change Score for Mottled Hyperpigmentation | 2.8 score on a scale | Standard Error 0.4 |
| Group A: No UV Exposure - Placebo | Clinical Change Score for Mottled Hyperpigmentation | .94 score on a scale | Standard Error 0.2 |
| Group A: No UV Exposure - No Treatment Control | Clinical Change Score for Mottled Hyperpigmentation | 0 score on a scale | Standard Error 0 |
Secondary
Gene Expression Changes as Assessed by Immunohistochemistry (IHC)
We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using IHC.
Time frame: Up to 6 months
Population: Data for this outcome measure was not collected.
Secondary
Gene Expression Changes as Assessed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR)
We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using RT-PCR.
Time frame: Up to 6 months
Population: Data for this outcome measure was not collected.