p53 ExpressionNCT04277949
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
A study testing Erbium:YAG and UV endonuclease from Micrococcus luteus in people with p53 Expression, run by Moy-Fincher-Chipps Facial Plastics and Dermatology.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- p53 Expression
- What is being tested?
- Erbium:YAG and UV endonuclease from Micrococcus luteus
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Apr 2020to Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- clinical signs of sun damage
- post-auricular regions have been visibly sun exposed
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effects of 2,940-nm Fractional Ablative Erbium and Topical DNA Repair Enzymes on p53 Epidermal Expression After 3 Months: A Comparative Clinical Trial
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
- Being tested
- Erbium:YAG, UV endonuclease from Micrococcus luteus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erbium:YAGDevice
Treatment with Erbium:YAG laser
UV endonuclease from Micrococcus luteusDrug
Application of topical DNA repair enzymes
| Study group | Role | What they receive |
|---|---|---|
| Erbium laser | Experimental | All participants will receive Erbium laser treatment on their right post-auricular region Receives: Device: Erbium:YAG |
| DNA repair enzyme | Experimental | All participants will apply topical DNA repair enzymes on their left post-auricular region Receives: Drug: UV endonuclease from Micrococcus luteus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2020
- Study startApr 2020 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for p53 ExpressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Moy-Fincher-Chipps Facial Plastics and Dermatology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04277949
- Sponsor's protocol ID
- 144156
- Status last verified
- Feb 2020
- First submitted
- 18 Feb 2020
- Last updated
- 20 Feb 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: We are currently in the process of determine the IPD sharing plan
Publications
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.
PubMed 12735636Berg 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.
PubMed 8552621Kanjilal 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.
PubMed 7627969Rees 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.
PubMed 7769252Orringer 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.
PubMed 15381546Liang 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.
PubMed 10190297Borges 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.
PubMed 29664771El-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.
PubMed 17550442Kabir 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.
PubMed 25738852Kuraoka I. Diversity of Endonuclease V: From DNA Repair to RNA Editing. Biomolecules. 2015 Sep 24;5(4):2194-206. doi: 10.3390/biom5042194.
PubMed 26404388Yarosh 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.
PubMed 11289350
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of 2,940-nm Fractional Ablative Erbium and Topical DNA Repair Enzymes on p53 Epidermal Expression After 3 Months: A Comparative Clinical Trial
- ClinicalTrials.gov ID
- NCT04277949
- Acronym / sponsor ID
- 144156
- Conditions
- p53 Expression
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Moy-Fincher-Chipps Facial Plastics and DermatologyUniversity, hospital or other
- Study start
- Apr 2020 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 20 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erbium laser | Experimental | Device: Erbium:YAGAll participants will receive Erbium laser treatment on their right post-auricular region |
| DNA repair enzyme | Experimental | Drug: UV endonuclease from Micrococcus luteusAll participants will apply topical DNA repair enzymes on their left post-auricular region |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- clinical signs of sun damage
- post-auricular regions have been visibly sun exposed
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erbium:YAGTreatment with Erbium:YAG laser | Device | Erbium laser |
| UV endonuclease from Micrococcus luteusApplication of topical DNA repair enzymes | Drug | DNA repair enzyme |
Primary outcome
p53 expression
Time frame: 3 months
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
- Background: PubMed 12735636El-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.
- Background: PubMed 8552621Berg 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.
- Background: PubMed 7627969Kanjilal 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.
- Background: PubMed 7769252Rees 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.
- Background: PubMed 15381546Orringer 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.
- Background: PubMed 10190297Liang 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.
- Background: PubMed 29664771Borges 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.
- Background: PubMed 17550442El-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.
- Background: PubMed 25738852Kabir 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.
- Background: PubMed 26404388Kuraoka I. Diversity of Endonuclease V: From DNA Repair to RNA Editing. Biomolecules. 2015 Sep 24;5(4):2194-206. doi: 10.3390/biom5042194.
- Background: PubMed 11289350Yarosh 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.
- Individual participant dataSharing planned: No. We are currently in the process of determine the IPD sharing plan
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing Erbium:YAG and UV endonuclease from Micrococcus luteus in people with p53 Expression, run by Moy-Fincher-Chipps Facial Plastics and Dermatology.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hiren Kolli, BS (5626594171, hiren@rodeoderm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
p53 expression (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04277949, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.