An Assessment of TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light

NCT05398237 | Completed Results DMC

• 2 other identifiers: 1907830098P01CA229112
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this project is to obtain clinical data, including skin samples, that will help investigators evaluate changes occurring in sun damaged human skin as a result of light that simulates sun exposure (Solar Simulated Light). Of specific interest are the molecular targets for cancer prevention. Molecular targets are the parts of the body's cells that have been shown to play a role in causing or preventing cancer and which scientists seek to affect in a way that may slow or eliminate the development of cancer.

Conditions

Sun Damaged Skin

Keywords

Solar Simulated Light; Sun Protected Skin; Sun Damaged Skin

Outcome Measures

Primary Outcomes (2)

• Number of TLR4 Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure)

  The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TLR4 signaling pathway (AKT S473, AKT T308, IkBa S32/36, IRAK2, IRF-3, IRF-3 S386, MyD88, TAK1 S412, TBK1/NAK, TLR4, TRAF3, TRAF6, TRIF, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.

  Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).

• Number of TOPK/PRPK Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure)

  The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TOPK/PRPK signaling pathway (p90RSK S380, PBK/TOPK, PRPK, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.

  Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).

Other Outcomes (1)

• Exploratory Endpoint: To Assess the Correlation Between Skin Sun Damage Level and the Magnitude of Solar Simulated Light-induced Pathway Activation.

  Baseline (pre-SSL exposure) and post-SSL exposure (at 5hr and 24hr post-exposure).

Study Arms (1)

TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light

EXPERIMENTAL

We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin.

Other: Solar Simulated Light (SSL)

Interventions

Solar Simulated Light (SSL) OTHER

Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.

TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy individuals 18 years of age or older.
• Individuals with mild, moderate, or severe photodamage \[1\] of the skin on the forearms (also Appendix C) and Fitzpatrick skin type II or III (21 CFR 352.72).
• Females of childbearing potential will need to undergo a pregnancy test at the enrollment visit, after administration of the informed consent form (ICF) and before exposure to SSL. Premenopausal female subjects must use an effective method of birth control (such as oral contraceptives, consistent use of barrier contraceptives, intrauterine device (IUD), or other proven method of birth control) during study participation. For the purposes of this study, a woman will be considered postmenopausal if any of the following criteria are met: (1) she has had prior bilateral oophorectomy; (2) she is over the age of 60 years; or (3) she is under the age of 60 years and has not had a menstrual period in 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression.
• Individuals who are willing to limit sun exposure to the body during the study period and who agree to wear protective clothing when they are outdoors.
• Individuals who have the ability to understand and willingness to sign an informed consent before initiation of study procedures, after the nature of the study is explained to them and they have had the opportunity to ask any questions.

You may not qualify if:

• Individuals with any inflammation or irritation of the skin at the test areas, or any skin conditions felt by the study medical provider to contraindicate enrollment. This includes, but is not limited to, psoriasis or atopic dermatitis within the test areas.
• Test area is defined as the 6 mm areas of skin that is exposed to SSL and will be biopsied.
• Individuals who have had invasive cancer, chemotherapy or radiation therapy within five years of study enrollment
• Individuals who are immunosuppressed by virtue of medication or disease. This includes AIDS patients, subjects taking oral steroids, and subjects on immunosuppressants/immunomodulators (cyclosporine, chemotherapeutic agents, or biologic therapy), as determined by the examining study medical provider.
• Individuals with serious intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness, or other situations that in the opinion of the examining study medical provider would limit compliance or interfere with the study regimen.
• Individuals who have used photosensitizing drugs (see Appendix for examples) within 30 days of enrollment, or who will be using a photosensitizing drug during the time of the study, will not be eligible. Subjects may be reconsidered for eligibility 30 days after the last dose of such medications.
• Individuals who have used any topical medication other than emollients or sunscreen/sunblock on the test area within 30 days prior to study enrollment. If a study participant requires topical medication to the test area during the study, they will be withdrawn from the study.
• Individuals who have used retinoids, steroids, 5-fluorouracil, Levulan, Vaniqua (eflornithine), Solaraze, or Imiquimod (Aldara®) anywhere on the body within 30 days prior to study enrollment. Subjects may be reconsidered for eligibility 30 days after the last topical treatment with such medications.
• Individuals must not take mega-doses of vitamins. Mega-doses are defined as more than 5 capsules of standard multivitamins daily or more than the Tolerable Upper Intake Levels of Vitamins, as defined by the Institute of Medicine, National Academy of Sciences. Such vitamin therapy must be discontinued at least 30 days prior to study entry.
• Individuals with a history of deliberate natural or artificial sun exposure (tanning) within 30 days of study enrollment are not eligible.
• Individuals with Fitzpatrick skin type I are ineligible, as the proposed SSL dose could result in a burn of greater than mild severity.
• Individuals with Fitzpatrick skin type IV, V or VI are ineligible, as they are unlikely to exhibit a salient response in the proposed design.
• Individuals currently enrolled in or who plan to enroll in another clinical trial. There must be a 30-day period between completing a previous study and enrolling in this study.
• Individuals with a known allergy to lidocaine are not eligible.
• Females who are pregnant or nursing.

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Results Point of Contact

• Title: Clara Curiel-Lewandrowski, MD
• Organization: University of Arizona Cancer Center

ccuriel@arizona.edu

(520) 626-5351

Study Officials

• Clara Curiel, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: May 31, 2022
• Study Start: February 3, 2020
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)