Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure

• ClinicalTrials.gov Identifier: NCT03126539
• Recruitment Status: Terminated
• First Posted: April 24, 2017
• Results First Posted: February 25, 2020
• Last Update Posted: February 25, 2020
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: April 7, 2017
• First Posted Date: April 24, 2017
• Results First Submitted Date: November 22, 2019
• Results First Posted Date: February 25, 2020
• Last Update Posted Date: February 25, 2020
• Actual Study Start Date: September 15, 2017
• Actual Primary Completion Date: January 25, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2020)

Clinical Change Score for Mottled Hyperpigmentation [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 20, 2017)

Quantitative RT-PCR and Immunohistochemistry to assess Keratin 16 and 17 induction in the basal epidermis. [ Time Frame: Within 6 months after last patient recruited. ]

We quantify the induction as measured by fold-change of keratin 16 and keratin 17 in the basal layer of the epidermis in both photoprotected and photodamaged skin treated with sulforaphane.

Current Secondary Outcome Measures (submitted: February 21, 2020)

• Gene Expression Changes as Assessed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: April 20, 2017)

Quantitative RT-PCR and Immunohistochemistry to assess gene expression changes [ Time Frame: Within 6 months after last patient recruited. ]

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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure
• Official Title: Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Aging

Intervention

• Drug: Sulforaphane
  Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway.
  Other Name: Broccoli sprout extract; isothiocyanate sulforaphane
• Radiation: Narrow-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).
  Other Name: UVB, UV
• Procedure: 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.
  Other Name: biopsy

Study Arms

• Experimental: Group A
  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.
  Interventions:

  • Drug: Sulforaphane
  • Procedure: 4 mm skin punch biopsy
• Experimental: Group B
  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.
  Interventions:

  • Drug: Sulforaphane
  • Radiation: Narrow-band Ultraviolet B exposure
  • Procedure: 4 mm skin punch biopsy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 14, 2019): 9
• Original Estimated Enrollment (submitted: April 20, 2017): 50
• Actual Study Completion Date: January 25, 2019
• Actual Primary Completion Date: January 25, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03126539
• Other Study ID Numbers: IRB00105668
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Johns Hopkins University
• Original Responsible Party: Same as current
• Current Study Sponsor: Johns Hopkins University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anna Chien; Johns Hopkins University

• PRS Account: Johns Hopkins University
• Verification Date: February 2020