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: June 30, 2022
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Aging	Drug: Sulforaphane; Radiation: Narrow-band Ultraviolet B exposure; Procedure: 4 mm skin punch biopsy	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure
• Actual Study Start Date: September 15, 2017
• Actual Primary Completion Date: January 25, 2019
• Actual Study Completion Date: January 25, 2019

Arms and Interventions

Arm	Intervention/treatment
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.	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; 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
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.	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Maryland

Cutaneous Translational Research Program, Department of Dermatology, Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Anna Chien; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] June 16, 2017

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03126539
• Other Study ID Numbers: IRB00105668
• First Posted: April 24, 2017
• Results First Posted: February 25, 2020
• Last Update Posted: June 30, 2022
• Last Verified: February 2020

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

Keywords provided by Johns Hopkins University:

aging; ultraviolet exposure; skin fragility; sulforaphane

Additional relevant MeSH terms:

Sulforaphane; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Antineoplastic Agents