To Evaluate and Compare p53 Epidermal Expression in Healthy Volunteers 3 Months After Treatment With a 2,940-nm Fractional Ablative Erbium Laser and Topical DNA Repair Enzymes

NCT04277949 | Unknown FDA Device

• 1 other identifier: 144156
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The p53 gene is located on the short arm of chromosome 17 and serves as a tumor suppressor gene. Alteration in p53 is an early event in skin cancer development. Further, p53 is the most commonly mutated gene in non-melanocytic skin cancers. The presence of p53 within epidermal skin cells is believed to reflect the malignant potential of photo-damaged skin. Studies have demonstrated that increasing sun exposure and age are directly associated with higher levels of p53 in facial skin. Consequently, the physiologic overexpression of p53 present in epidermal skin may be indicative of both past photodamage and future risk for developing skin cancer. Advancements in dermatologic research have allowed clinicians to treat photo-damaged skin with with novel modalities. For example, epidermal ablation with the 2,940nm fractional erbium laser has been shown to reduce the risk of carcinogenesis by promoting apoptosis, working similarly to p53. Laser resurfacing results in the replacement of epidermal cells once the necrotic debris is cleared away. This therapeutic effect of laser resurfacing may be gauged by cutaneous p53 expression before and after such interventions. Investigators have noted the reliability of cutaneous p53 expression to gauge therapeutic effects in patients receiving erbium doped yttrium aluminum garnet laser (Er:YAG), dermabrasion, and CO2 laser. Similarly to laser resurfacing, topical DNA repair enzymes have been shown to be protective against skin cancer development and, therefore, may also reduce epidermal p53 expression. UV endonuclease, a DNA repair enzyme derived from the UV-resistant microbe Micrococcus luteus, enhances DNA repair by removing cyclobutane pyrimidine dimers (CPDs) induced by ultraviolet radiation (UVR). To efficiently penetrate the stratum corneum, this enzyme is encapsulated within liposomes, which facilitate entry into keratinocyte nuclei. Once exposed to CPDs, UV endonuclease repairs DNA by catalyzing two reactions: the first uses glycosylase, which releases thymine and causes an apurinic site; the second involves lyase, which incises the phosphodiester backbone, causing a single stranded break. An exonuclease then removes bases around this site, and a polymerase fills the gap, thereby repairing the photodamaged DNA. In addition to repairing damaged DNA on the molecular level, UV endonuclease has also demonstrated the ability to clinically decrease non-melanocytic skin cancer and pre-cancer development. The capability of topical DNA repair enzymes to reverse DNA damage leads us to believe that it will also lead to a reduction in p53 expression within epidermal cells. For these reasons, we wish to investigate the role of 2,940 fractional erbium laser and topical DNA repair enzymes on reducing cutaneous p53 expression.

Conditions

p53 Expression

Outcome Measures

Primary Outcomes (1)

• p53 expression

  p53 epidermal expression will be evaluated by scoring the nuclear staining of basilar cells in 3-mm punch biopsies, knowing that the basal layer gives rise to dysplasia. The numbers of stained cells present at the 3-month visit will be compared with the number of stained cells present at the baseline visit.

  3 months

Study Arms (2)

Erbium laser

EXPERIMENTAL

All participants will receive Erbium laser treatment on their right post-auricular region

Device: Erbium:YAG

DNA repair enzyme

EXPERIMENTAL

All participants will apply topical DNA repair enzymes on their left post-auricular region

Drug: UV endonuclease from Micrococcus luteus

Interventions

Erbium:YAG DEVICE

Treatment with Erbium:YAG laser

Erbium laser

UV endonuclease from Micrococcus luteus DRUG

Application of topical DNA repair enzymes

DNA repair enzyme

Eligibility Criteria

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

You may qualify if:

• clinical signs of sun damage
• post-auricular regions have been visibly sun exposed

You may not qualify if:

• history of actinic keratoses or skin cancer on tested site
• active tanning
• currently taking hormonal replacement therapy
• using topical or oral treatments for for photo aging in previous 6 months
• are currently pregnant or lactating

Sponsors & Collaborators

• Moy-Fincher-Chipps Facial Plastics and Dermatology: lead

Related Publications (11)

• El-Domyati MB, Attia S, Saleh F, Galaria N, Ahmad H, Gasparro FP, Uitto J. Expression of p53 in normal sun-exposed and protected skin (type IV-V) in different decades of age. Acta Derm Venereol. 2003;83(2):98-104. doi: 10.1080/00015550310007427.

  PMID: 12735636 BACKGROUND

• Berg RJ, van Kranen HJ, Rebel HG, de Vries A, van Vloten WA, Van Kreijl CF, van der Leun JC, de Gruijl FR. Early p53 alterations in mouse skin carcinogenesis by UVB radiation: immunohistochemical detection of mutant p53 protein in clusters of preneoplastic epidermal cells. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):274-8. doi: 10.1073/pnas.93.1.274.

  PMID: 8552621 BACKGROUND

• Kanjilal S, Strom SS, Clayman GL, Weber RS, el-Naggar AK, Kapur V, Cummings KK, Hill LA, Spitz MR, Kripke ML, et al. p53 mutations in nonmelanoma skin cancer of the head and neck: molecular evidence for field cancerization. Cancer Res. 1995 Aug 15;55(16):3604-9.

  PMID: 7627969 BACKGROUND

• Rees JL. p53 and the origins of skin cancer. J Invest Dermatol. 1995 Jun;104(6):883-4. doi: 10.1111/1523-1747.ep12606149. No abstract available.

  PMID: 7769252 BACKGROUND

• Orringer JS, Johnson TM, Kang S, Karimipour DJ, Hammerberg C, Hamilton T, Voorhees JJ, Fisher GJ. Effect of carbon dioxide laser resurfacing on epidermal p53 immunostaining in photodamaged skin. Arch Dermatol. 2004 Sep;140(9):1073-7. doi: 10.1001/archderm.140.9.1073.

  PMID: 15381546 BACKGROUND

• Liang SB, Ohtsuki Y, Furihata M, Takeuchi T, Iwata J, Chen BK, Sonobe H. Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer. Virchows Arch. 1999 Mar;434(3):193-9. doi: 10.1007/s004280050327.

  PMID: 10190297 BACKGROUND

• Borges J, Araujo L, de Oliveira RPB, Manela-Azulay M. Effects of 1,540-nm Fractional Nonablative Erbium and 2,940-nm Fractional Ablative Erbium on p53 Epidermal Expression After 3 months: A Split-Face Interventional Study. Dermatol Surg. 2018 Aug;44(8):1109-1114. doi: 10.1097/DSS.0000000000001527.

  PMID: 29664771 BACKGROUND

• El-Domyati MM, Attia SK, Esmat AM, Ahmad HM, Abdel Wahab HM, Badr BM. Effect of laser resurfacing on p53 expression in photoaged facial skin. Dermatol Surg. 2007 Jun;33(6):668-75. doi: 10.1111/j.1524-4725.2007.33141.x.

  PMID: 17550442 BACKGROUND

• Kabir Y, Seidel R, Mcknight B, Moy R. DNA repair enzymes: an important role in skin cancer prevention and reversal of photodamage--a review of the literature. J Drugs Dermatol. 2015 Mar;14(3):297-303.

  PMID: 25738852 BACKGROUND

• Kuraoka I. Diversity of Endonuclease V: From DNA Repair to RNA Editing. Biomolecules. 2015 Sep 24;5(4):2194-206. doi: 10.3390/biom5042194.

  PMID: 26404388 BACKGROUND

• Yarosh D, Klein J, O'Connor A, Hawk J, Rafal E, Wolf P. Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet. 2001 Mar 24;357(9260):926-9. doi: 10.1016/s0140-6736(00)04214-8.

  PMID: 11289350 BACKGROUND

Central Study Contacts

Hiren Kolli, BS

CONTACT

5626594171; hiren@rodeoderm.com

Study Design

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

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 20, 2020
• Study Start: April 1, 2020
• Primary Completion: June 1, 2020
• Study Completion: August 1, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share