Actinic CheilitisPhase 1NCT04219358
Topical Application of Imiquimod Gel at Different Concentrations in Actinic Cheilitis
A Phase 1 study testing Imiquimod 5% gel, Imiquimod 0,05% gel and Imiquimod nanoencapsulated 0,05% gel in people with Actinic Cheilitis, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
Trial summary
Actinic cheilitis is a potentially malignant lesion on the lower lip, which can progress to more serious illnesses such as cancer if not treated. Usually treatment of this condition is only based on clinical appearance, but there is no established cure treatment. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Actinic Cheilitis
- What is being tested?
- Imiquimod 5% gel, Imiquimod 0,05% gel and Imiquimod nanoencapsulated 0,05% gel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 2 sitesBrazil
- Study dates
- 23 Mar 2019to 24 Aug 2021
- Phase
- Phase 1
- 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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Individuals with clinical and histopathological diagnosis of actinic cheilitis;
- No previous lip treatment with Imiquimod.
Who cannot join
- Present lesions suspected of squamous cell carcinoma of the lip.
- Previous history of lip cancer treatment.
- Prior treatment other than standard treatment.
- History of allergic reactions to imiquimod or any other component of the formulas.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90040-060
School of Dentistry - Universidade Federal do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90040-060
About this study
Official title: Evaluation of Topical Application of 5% Imiquimod, 0.05% Imiquimod and 0.05% Nanoencapsulated Imiquimod Gel in the Treatment of Actinic Cheilitis: a Randomized Controlled Trial
Actinic cheilitis is a potentially malignant lesion on the lower lip, which can progress to more serious illnesses such as cancer if not treated. Usually treatment of this condition is only based on clinical appearance, but there is no established cure treatment. Topical imiquimod is a medicine indicated for the treatment of skin diseases, but it has not yet been proven to treat actinic cheilitis. In this research, the investigator's aim is to evaluate the response to actinic cheilitis treatment with the current standard treatment compared to high and low concentration imiquimod topical formulations.
Read the detailed description
Three formulations are used in this research: imiquimod 5%, imiquimod 0.05% e imiquimod nanoencapsulated 0.05%. Nanoencapsulation is a process that concentrates the drug into a capsule not visible to the naked eye, allowing it to penetrate skin more easily and will only release the drug at the lesion site. The drug is presented in a free form inside the gel in the others formulations.
- Conditions
- Actinic Cheilitis
- Being tested
- Vehicle Gel Base, Imiquimod 5% gel, Imiquimod 0,05% gel, Imiquimod nanoencapsulated 0,05% gel, Lip sunscreen 30 Sun Protector Factor (SPF)
- Keywords
- imiquimod, nanoencapsulation
- Medical subject headings
- Actinic cheilitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vehicle Gel BaseDrug
Apply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks.
Gel components: medium molecular weight chitosan, lactic acid 85% and water.
Imiquimod 5% gelDrug
Apply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks.
Gel components: medium molecular weight chitosan, lactic acid 85% and free form imiquimod 5%.
Imiquimod 0,05% gelDrug
Apply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks.
Gel components: medium molecular weight chitosan, lactic acid 85% and imiquimod 0.05% free form.
Imiquimod nanoencapsulated 0,05% gelDrug
Apply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks.
Gel components: medium molecular weight chitosan, lactic acid 85% and imiquomod in a nanoencapsulated suspension at concentration of 0,05%
Lip sunscreen 30 Sun Protector Factor (SPF)Drug
Apply sunscreen on the lip 30 minutes every day before sun exposure. Protects against both UVA (ultraviolet A) and UVB (ultraviolet B rays).
DexpanthenolDrug
Apply dexpanthenol on the lip, two (2) times a day, once in the morning and once in the afternoon.
Reduces transepidermic water loss and maintaining the natural smoothness and elasticity of the skin. It accelerates the cell renewal, rebuilds damaged tissues and promote the normal keratinisation of the skin and hair.
| Study group | Role | What they receive |
|---|---|---|
| Placebo & Standard Treatment | Active comparator | Not described Receives: Drug: Vehicle Gel Base; Drug: Lip sunscreen 30 Sun Protector Factor (SPF); Drug: Dexpanthenol |
| Imiquimod 5% & Standard Treatment | Experimental | Not described Receives: Drug: Imiquimod 5% gel; Drug: Lip sunscreen 30 Sun Protector Factor (SPF); Drug: Dexpanthenol |
| Imiquimod 0.05% & Standard Treatment | Experimental | Not described Receives: Drug: Imiquimod 0,05% gel; Drug: Lip sunscreen 30 Sun Protector Factor (SPF); Drug: Dexpanthenol |
| Imiquimod nanoencapsulated 0.05% & Standard Treatment | Experimental | Not described Receives: Drug: Imiquimod nanoencapsulated 0,05% gel; Drug: Lip sunscreen 30 Sun Protector Factor (SPF); Drug: Dexpanthenol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response
Clinical analysis of lip photographs based on a classification. The lesions will be graded as:
AC Grade I. Dryness and desquamation on the vermilion of lips.
AC Grade II. Atrophy on the vermilion's border, presenting soft surfaces and pallid areas with eruptions. Blurred limit between the lip's vermilion border and the skin, or a dark line demarking that limit can be seen. This melanotic line should be different from ephelides or other pigmented lesions.
AC Grade III. Rough and squamous areas on the drier parts of the vermilion and hyperkeratotic areas, especially when they spread to the wet lip's mucosa (border between mucosa and semimucosa).
AC Grade IV. Ulceration present in one or more sites of the lip's vermillion or Leukoplakia, mainly in more traumatic places, due to the history of pipe or cigarettes consumption. These lesions could suggest that a malignization process would be in progress, especially when they are accompanied by endured areas on palpation.
Measured: 30 days after conclusion of treatment
Clinical Response
Clinical analysis of lip photographs based on a classification. The lesions will be graded as:
AC Grade I. Dryness and desquamation on the vermilion of lips.
AC Grade II. Atrophy on the vermilion's border, presenting soft surfaces and pallid areas with eruptions. Blurred limit between the lip's vermilion border and the skin, or a dark line demarking that limit can be seen. This melanotic line should be different from ephelides or other pigmented lesions.
AC Grade III. Rough and squamous areas on the drier parts of the vermilion and hyperkeratotic areas, especially when they spread to the wet lip's mucosa (border between mucosa and semimucosa).
AC Grade IV. Ulceration present in one or more sites of the lip's vermillion or Leukoplakia, mainly in more traumatic places, due to the history of pipe or cigarettes consumption. These lesions could suggest that a malignization process would be in progress, especially when they are accompanied by endured areas on palpation.
Measured: 180 days after conclusion of treatment
Secondary outcomes (17)
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Satisfaction will be self-reported by VAS scale. The visual analogue scale (VAS) will be used to measure general satisfaction of participants to treatment. Participants will be asked to point in to a white paper with a 10cm line, where 0 represents none satisfaction and 10 maximum satisfaction.
Measured: VAS scale will be generated at 14 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Satisfaction will be self-reported by VAS scale. The visual analogue scale (VAS) will be used to measure general satisfaction of participants to treatment. Participants will be asked to point in to a white paper with a 10cm line, where 0 represents none satisfaction and 10 maximum satisfaction.
Measured: VAS scale will be generated at 28 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Satisfaction will be self-reported by VAS scale. The visual analogue scale (VAS) will be used to measure general satisfaction of participants to treatment. Participants will be asked to point in to a white paper with a 10cm line, where 0 represents none satisfaction and 10 maximum satisfaction.
Measured: VAS scale will be generated at 60 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Satisfaction will be self-reported by VAS scale. The visual analogue scale (VAS) will be used to measure general satisfaction of participants to treatment. Participants will be asked to point in to a white paper with a 10cm line, where 0 represents none satisfaction and 10 maximum satisfaction.
Measured: VAS scale will be generated at 210 days after beginning of the treatment.
Adverse Events Severity
Adverse effects will be assessed during clinical evaluation at follow-up and with an adverse effects questionnaire.The questionnaire is based on self-reported events followed by a quantification of severity of local and systemic events. The participants are asked to classify the events in a scale of 0 to 3. 0= no sympton, 1- mild, 2-moderate and 3-severe.
Measured: The adverse events questionnaire is applied in 14 days after beginning of the treatment.
Adverse Events Severity
Adverse effects will be assessed during clinical evaluation at follow-up and with an adverse effects questionnaire.The questionnaire is based on self-reported events followed by a quantification of severity of local and systemic events. The participants are asked to classify the events in a scale of 0 to 3. 0= no sympton, 1- mild, 2-moderate and 3-severe.
Measured: The adverse events questionnaire is applied in 28 days after beginning of the treatment.
Adverse Events Severity
Adverse effects will be assessed during clinical evaluation at follow-up and with an adverse effects questionnaire.The questionnaire is based on self-reported events followed by a quantification of severity of local and systemic events. The participants are asked to classify the events in a scale of 0 to 3. 0= no sympton, 1- mild, 2-moderate and 3-severe.
Measured: The adverse events questionnaire is applied in 60 days after beginning of the treatment.
Adverse Events Severity
Adverse effects will be assessed during clinical evaluation at follow-up and with an adverse effects questionnaire.The questionnaire is based on self-reported events followed by a quantification of severity of local and systemic events. The participants are asked to classify the events in a scale of 0 to 3. 0= no sympton, 1- mild, 2-moderate and 3-severe.
Measured: The adverse events questionnaire is applied in 210 days after beginning of the treatment.
Maturation epithelial pattern
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. With this examination it is possible to analyze morphological changes of the collected cells by light microscopy. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. From one of the obtained smears, Papanicolaou stain will be performed. Papanicoloau staining allows assessing different cell types, which are quantified to evaluate epithelial differentiation.
Measured: Maturation epithelial pattern analysis will be performed at 28 days after beginning of the treatment.
Maturation epithelial pattern
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. With this examination it is possible to analyze morphological changes of the collected cells by light microscopy. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. From one of the obtained smears, Papanicolaou stain will be performed. Papanicoloau staining allows assessing different cell types, which are quantified to evaluate epithelial differentiation.
Measured: Maturation epithelial pattern analysis will be performed at 60 days after beginning of the treatment.
Maturation epithelial pattern
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. With this examination it is possible to analyze morphological changes of the collected cells by light microscopy. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. From one of the obtained smears, Papanicolaou stain will be performed. Papanicoloau staining allows assessing different cell types, which are quantified to evaluate epithelial differentiation.
Measured: Maturation epithelial pattern analysis will be performed at 210 days after beginning of the treatment.
Cell proliferation - mAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. From the quantification of AgNORs, the average AgNORs / core (mAgNOR) will be calculated. The low average of AgNOR stained cells indicates lower cell proliferation and a higher average indicates greater proliferation.
Measured: mAgNOR analysis will be performed at 28 days after beginning of the treatment.
Cell proliferation - mAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. From the quantification of AgNORs, the average AgNORs / core (mAgNOR) will be calculated. The low average of AgNOR stained cells indicates lower cell proliferation and a higher average indicates greater proliferation.
Measured: mAgNOR analysis will be performed at 60 days after beginning of the treatment.
Cell proliferation - mAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. From the quantification of AgNORs, the average AgNORs / core (mAgNOR) will be calculated. The low average of AgNOR stained cells indicates lower cell proliferation and a higher average indicates greater proliferation.
Measured: mAgNOR analysis will be performed at 210 days after beginning of the treatment.
Cell proliferation - pAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. A second evaluation parameter will be the percentage of cells with more than 1, 2, 3 and 4 AgNORs / nucleus (pAgNOR). A higher percentage of cells with more than 3 and 4 AgNORs per nucleus indicate greater proliferation.
Measured: pAgNOR analysis will be performed at 28 days after beginning of the treatment.
Cell proliferation - pAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. A second evaluation parameter will be the percentage of cells with more than 1, 2, 3 and 4 AgNORs / nucleus (pAgNOR). A higher percentage of cells with more than 3 and 4 AgNORs per nucleus indicate greater proliferation.
Measured: pAgNOR analysis will be performed at 60 days after beginning of the treatment.
Cell proliferation - pAgNOR
Upon confirmation of the diagnosis of actinic cheilitis, participants will undergo a noninvasive procedure called exfoliative cytology. The lip mucosa is scraped with cytobrush, which is then used to smear two glass slides. One slide will be stained with AgNOR. With this examination it is possible to analyze cell proliferation activity. A second evaluation parameter will be the percentage of cells with more than 1, 2, 3 and 4 AgNORs / nucleus (pAgNOR). A higher percentage of cells with more than 3 and 4 AgNORs per nucleus indicate greater proliferation.
Measured: pAgNOR analysis will be performed at 210 days after beginning of the treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start23 Mar 2019
- Primary completion24 Jun 2020
- Study completion24 Aug 2021
Why it stopped: Study terminated because of COVID19 pandemics.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Actinic CheilitisStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Federal University of Rio Grande do Sul
- Responsible party
- Sponsor
- Investigators
- Fernanda Visioli, PhD, Principal investigator, Federal University of Rio Grande do Sul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04219358
- Sponsor's protocol ID
- 2018-0656
- Status last verified
- Nov 2022
- First submitted
- 4 Oct 2019
- Last updated
- 22 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Poitevin NA, Rodrigues MS, Weigert KL, Macedo CLR, Dos Santos RB. Actinic cheilitis: proposition and reproducibility of a clinical criterion. BDJ Open. 2017 Aug 4;3:17016. doi: 10.1038/bdjopen.2017.16. eCollection 2017.
PubMed 29607086Bernardi A, Frozza RL, Jager E, Figueiro F, Bavaresco L, Salbego C, Pohlmann AR, Guterres SS, Battastini AM. Selective cytotoxicity of indomethacin and indomethacin ethyl ester-loaded nanocapsules against glioma cell lines: an in vitro study. Eur J Pharmacol. 2008 May 31;586(1-3):24-34. doi: 10.1016/j.ejphar.2008.02.026. Epub 2008 Feb 19.
PubMed 18371953Bernardi A, Zilberstein AC, Jager E, Campos MM, Morrone FB, Calixto JB, Pohlmann AR, Guterres SS, Battastini AM. Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. Br J Pharmacol. 2009 Oct;158(4):1104-11. doi: 10.1111/j.1476-5381.2009.00244.x. Epub 2009 May 6.
PubMed 19422380Bernardi A, Braganhol E, Jager E, Figueiro F, Edelweiss MI, Pohlmann AR, Guterres SS, Battastini AM. Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model. Cancer Lett. 2009 Aug 18;281(1):53-63. doi: 10.1016/j.canlet.2009.02.018. Epub 2009 Mar 14.
PubMed 19286307Swanson N, Abramovits W, Berman B, Kulp J, Rigel DS, Levy S. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol. 2010 Apr;62(4):582-90. doi: 10.1016/j.jaad.2009.07.004. Epub 2010 Feb 4.
PubMed 20133013Sotiriou E, Lallas A, Goussi C, Apalla Z, Trigoni A, Chovarda E, Ioannides D. Sequential use of photodynamic therapy and imiquimod 5% cream for the treatment of actinic cheilitis: a 12-month follow-up study. Br J Dermatol. 2011 Oct;165(4):888-92. doi: 10.1111/j.1365-2133.2011.10478.x. Epub 2011 Sep 15.
PubMed 21916880Smith KJ, Germain M, Yeager J, Skelton H. Topical 5% imiquimod for the therapy of actinic cheilitis. J Am Acad Dermatol. 2002 Oct;47(4):497-501. doi: 10.1067/mjd.2002.126266.
PubMed 12271290McDonald C, Laverick S, Fleming CJ, White SJ. Treatment of actinic cheilitis with imiquimod 5% and a retractor on the lower lip: clinical and histological outcomes in 5 patients. Br J Oral Maxillofac Surg. 2010 Sep;48(6):473-6. doi: 10.1016/j.bjoms.2009.08.024.
PubMed 19836865Manganaro AM, Will MJ, Poulos E. Actinic cheilitis: a premalignant condition. Gen Dent. 1997 Sep-Oct;45(5):492-4.
PubMed 9515418Lundeen RC, Langlais RP, Terezhalmy GT. Sunscreen protection for lip mucosa: a review and update. J Am Dent Assoc. 1985 Oct;111(4):617-21. doi: 10.14219/jada.archive.1985.0157.
PubMed 3877087Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH, Fox TL. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol. 2004 May;50(5):714-21. doi: 10.1016/j.jaad.2003.12.010.
PubMed 15097955Krawtchenko N, Roewert-Huber J, Ulrich M, Mann I, Sterry W, Stockfleth E. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007 Dec;157 Suppl 2:34-40. doi: 10.1111/j.1365-2133.2007.08271.x.
PubMed 18067630Kopera D, Kerl H. Visualization and treatment of subclinical actinic keratoses with topical imiquimod 5% cream: an observational study. Biomed Res Int. 2014;2014:135916. doi: 10.1155/2014/135916. Epub 2014 May 11.
PubMed 24900953Kaugars GE, Pillion T, Svirsky JA, Page DG, Burns JC, Abbey LM. Actinic cheilitis: a review of 152 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999 Aug;88(2):181-6. doi: 10.1016/s1079-2104(99)70115-0.
PubMed 10468463Jorizzo J, Dinehart S, Matheson R, Moore JK, Ling M, Fox TL, McRae S, Fielder S, Lee JH. Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. J Am Acad Dermatol. 2007 Aug;57(2):265-8. doi: 10.1016/j.jaad.2007.01.047. Epub 2007 May 18.
PubMed 17512087
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Topical Application of 5% Imiquimod, 0.05% Imiquimod and 0.05% Nanoencapsulated Imiquimod Gel in the Treatment of Actinic Cheilitis: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04219358
- Acronym / sponsor ID
- 2018-0656
- Conditions
- Actinic Cheilitis
- Keywords
- imiquimod, nanoencapsulation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated because of COVID19 pandemics.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Federal University of Rio Grande do Sul
- Study start
- 23 Mar 2019 (actual)
- Primary completion
- 24 Jun 2020 (actual)
- Study completion
- 24 Aug 2021 (actual)
- First posted
- 7 Jan 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.
Actinic cheilitis is a potentially malignant lesion on the lower lip, which can progress to more serious illnesses such as cancer if not treated. Usually treatment of this condition is only based on clinical appearance, but there is no established cure treatment. Topical imiquimod is a medicine indicated for the treatment of skin diseases, but it has not yet been proven to treat actinic cheilitis. In this research, the investigator's aim is to evaluate the response to actinic cheilitis treatment with the current standard treatment compared to high and low concentration imiquimod topical formulations.
Detailed description
Three formulations are used in this research: imiquimod 5%, imiquimod 0.05% e imiquimod nanoencapsulated 0.05%. Nanoencapsulation is a process that concentrates the drug into a capsule not visible to the naked eye, allowing it to penetrate skin more easily and will only release the drug at the lesion site. The drug is presented in a free form inside the gel in the others formulations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo & Standard Treatment | Active comparator | Drug: Vehicle Gel Base, Drug: Lip sunscreen 30 Sun Protector Factor (SPF), Drug: Dexpanthenol |
| Imiquimod 5% & Standard Treatment | Experimental | Drug: Imiquimod 5% gel, Drug: Lip sunscreen 30 Sun Protector Factor (SPF), Drug: Dexpanthenol |
| Imiquimod 0.05% & Standard Treatment | Experimental | Drug: Imiquimod 0,05% gel, Drug: Lip sunscreen 30 Sun Protector Factor (SPF), Drug: Dexpanthenol |
| Imiquimod nanoencapsulated 0.05% & Standard Treatment | Experimental | Drug: Imiquimod nanoencapsulated 0,05% gel, Drug: Lip sunscreen 30 Sun Protector Factor (SPF), Drug: Dexpanthenol |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Individuals with clinical and histopathological diagnosis of actinic cheilitis;
- No previous lip treatment with Imiquimod.
Key exclusion criteria (4 listed)
- Present lesions suspected of squamous cell carcinoma of the lip.
- Previous history of lip cancer treatment.
- Prior treatment other than standard treatment.
- History of allergic reactions to imiquimod or any other component of the formulas.
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 |
|---|---|---|
| Vehicle Gel BaseApply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks. Gel components: medium molecular weight chitosan, lactic acid 85% and water. | Drug | Placebo & Standard Treatment |
| Imiquimod 5% gelApply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks. Gel components: medium molecular weight chitosan, lactic acid 85% and free form imiquimod 5%. | Drug | Imiquimod 5% & Standard Treatment |
| Imiquimod 0,05% gelApply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks. Gel components: medium molecular weight chitosan, lactic acid 85% and imiquimod 0.05% free form. | Drug | Imiquimod 0.05% & Standard Treatment |
| Imiquimod nanoencapsulated 0,05% gelApply 0.5ml of gel stored in a 1ml syringe over the lip 3 times a week (Mondays, Wednesdays and Fridays) at night for a period of 4 weeks. Gel components: medium molecular weight chitosan, lactic acid 85% and imiquomod in a nanoencapsulated suspension at concentration of 0,05% | Drug | Imiquimod nanoencapsulated 0.05% & Standard Treatment |
| Lip sunscreen 30 Sun Protector Factor (SPF)Apply sunscreen on the lip 30 minutes every day before sun exposure. Protects against both UVA (ultraviolet A) and UVB (ultraviolet B rays). | Drug | Imiquimod 0.05% & Standard Treatment, Imiquimod 5% & Standard Treatment, Imiquimod nanoencapsulated 0.05% & Standard Treatment, Placebo & Standard Treatment |
| DexpanthenolApply dexpanthenol on the lip, two (2) times a day, once in the morning and once in the afternoon. Reduces transepidermic water loss and maintaining the natural smoothness and elasticity of the skin. It accelerates the cell renewal, rebuilds damaged tissues and promote the normal keratinisation of the skin and hair. | Drug | Imiquimod 0.05% & Standard Treatment, Imiquimod 5% & Standard Treatment, Imiquimod nanoencapsulated 0.05% & Standard Treatment, Placebo & Standard Treatment |
Primary outcome
Clinical Response
Time frame: 30 days after conclusion of treatment
Clinical analysis of lip photographs based on a classification. The lesions will be graded as: AC Grade I. Dryness and desquamation on the vermilion of lips. AC Grade II. Atrophy on the vermilion's border, presenting soft surfaces and pallid areas with eruptions. Blurred limit between the lip's vermilion border and the skin, or a dark line demarking that limit can be seen. This melanotic line should be different from ephelides or other pigmented lesions. AC Grade III. Rough and squamous areas on the drier parts of the vermilion and hyperkeratotic areas, especially when they spread to the wet lip's mucosa (border between mucosa and semimucosa). AC Grade IV. Ulceration present in one or more sites of the lip's vermillion or Leukoplakia, mainly in more traumatic places, due to the history of pipe or cigarettes consumption. These lesions could suggest that a malignization process would be in progress, especially when they are accompanied by endured areas on palpation.
Clinical Response
Time frame: 180 days after conclusion of treatment
Clinical analysis of lip photographs based on a classification. The lesions will be graded as: AC Grade I. Dryness and desquamation on the vermilion of lips. AC Grade II. Atrophy on the vermilion's border, presenting soft surfaces and pallid areas with eruptions. Blurred limit between the lip's vermilion border and the skin, or a dark line demarking that limit can be seen. This melanotic line should be different from ephelides or other pigmented lesions. AC Grade III. Rough and squamous areas on the drier parts of the vermilion and hyperkeratotic areas, especially when they spread to the wet lip's mucosa (border between mucosa and semimucosa). AC Grade IV. Ulceration present in one or more sites of the lip's vermillion or Leukoplakia, mainly in more traumatic places, due to the history of pipe or cigarettes consumption. These lesions could suggest that a malignization process would be in progress, especially when they are accompanied by endured areas on palpation.
17 secondary outcomes
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Time frame: VAS scale will be generated at 14 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Time frame: VAS scale will be generated at 28 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Time frame: VAS scale will be generated at 60 days after beginning of the treatment.
General Satisfaction about the medication: Visual Analogue Scale (VAS)
Time frame: VAS scale will be generated at 210 days after beginning of the treatment.
Adverse Events Severity
Time frame: The adverse events questionnaire is applied in 14 days after beginning of the treatment.
Adverse Events Severity
Time frame: The adverse events questionnaire is applied in 28 days after beginning of the treatment.
Adverse Events Severity
Time frame: The adverse events questionnaire is applied in 60 days after beginning of the treatment.
Adverse Events Severity
Time frame: The adverse events questionnaire is applied in 210 days after beginning of the treatment.
Maturation epithelial pattern
Time frame: Maturation epithelial pattern analysis will be performed at 28 days after beginning of the treatment.
Maturation epithelial pattern
Time frame: Maturation epithelial pattern analysis will be performed at 60 days after beginning of the treatment.
Maturation epithelial pattern
Time frame: Maturation epithelial pattern analysis will be performed at 210 days after beginning of the treatment.
Cell proliferation - mAgNOR
Time frame: mAgNOR analysis will be performed at 28 days after beginning of the treatment.
Cell proliferation - mAgNOR
Time frame: mAgNOR analysis will be performed at 60 days after beginning of the treatment.
Cell proliferation - mAgNOR
Time frame: mAgNOR analysis will be performed at 210 days after beginning of the treatment.
Cell proliferation - pAgNOR
Time frame: pAgNOR analysis will be performed at 28 days after beginning of the treatment.
Cell proliferation - pAgNOR
Time frame: pAgNOR analysis will be performed at 60 days after beginning of the treatment.
Cell proliferation - pAgNOR
Time frame: pAgNOR analysis will be performed at 210 days after beginning of the treatment.
Results and safety
The study was stopped early (reason given: Study terminated because of COVID19 pandemics.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2022.
- Background: PubMed 29607086Poitevin NA, Rodrigues MS, Weigert KL, Macedo CLR, Dos Santos RB. Actinic cheilitis: proposition and reproducibility of a clinical criterion. BDJ Open. 2017 Aug 4;3:17016. doi: 10.1038/bdjopen.2017.16. eCollection 2017.
- Background: PubMed 18371953Bernardi A, Frozza RL, Jager E, Figueiro F, Bavaresco L, Salbego C, Pohlmann AR, Guterres SS, Battastini AM. Selective cytotoxicity of indomethacin and indomethacin ethyl ester-loaded nanocapsules against glioma cell lines: an in vitro study. Eur J Pharmacol. 2008 May 31;586(1-3):24-34. doi: 10.1016/j.ejphar.2008.02.026. Epub 2008 Feb 19.
- Background: PubMed 19422380Bernardi A, Zilberstein AC, Jager E, Campos MM, Morrone FB, Calixto JB, Pohlmann AR, Guterres SS, Battastini AM. Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. Br J Pharmacol. 2009 Oct;158(4):1104-11. doi: 10.1111/j.1476-5381.2009.00244.x. Epub 2009 May 6.
- Background: PubMed 19286307Bernardi A, Braganhol E, Jager E, Figueiro F, Edelweiss MI, Pohlmann AR, Guterres SS, Battastini AM. Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model. Cancer Lett. 2009 Aug 18;281(1):53-63. doi: 10.1016/j.canlet.2009.02.018. Epub 2009 Mar 14.
- Background: PubMed 20133013Swanson N, Abramovits W, Berman B, Kulp J, Rigel DS, Levy S. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol. 2010 Apr;62(4):582-90. doi: 10.1016/j.jaad.2009.07.004. Epub 2010 Feb 4.
- Background: PubMed 21916880Sotiriou E, Lallas A, Goussi C, Apalla Z, Trigoni A, Chovarda E, Ioannides D. Sequential use of photodynamic therapy and imiquimod 5% cream for the treatment of actinic cheilitis: a 12-month follow-up study. Br J Dermatol. 2011 Oct;165(4):888-92. doi: 10.1111/j.1365-2133.2011.10478.x. Epub 2011 Sep 15.
- Background: PubMed 12271290Smith KJ, Germain M, Yeager J, Skelton H. Topical 5% imiquimod for the therapy of actinic cheilitis. J Am Acad Dermatol. 2002 Oct;47(4):497-501. doi: 10.1067/mjd.2002.126266.
- Background: PubMed 19836865McDonald C, Laverick S, Fleming CJ, White SJ. Treatment of actinic cheilitis with imiquimod 5% and a retractor on the lower lip: clinical and histological outcomes in 5 patients. Br J Oral Maxillofac Surg. 2010 Sep;48(6):473-6. doi: 10.1016/j.bjoms.2009.08.024.
- Background: PubMed 9515418Manganaro AM, Will MJ, Poulos E. Actinic cheilitis: a premalignant condition. Gen Dent. 1997 Sep-Oct;45(5):492-4.
- Background: PubMed 3877087Lundeen RC, Langlais RP, Terezhalmy GT. Sunscreen protection for lip mucosa: a review and update. J Am Dent Assoc. 1985 Oct;111(4):617-21. doi: 10.14219/jada.archive.1985.0157.
- Background: PubMed 15097955Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH, Fox TL. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol. 2004 May;50(5):714-21. doi: 10.1016/j.jaad.2003.12.010.
- Background: PubMed 18067630Krawtchenko N, Roewert-Huber J, Ulrich M, Mann I, Sterry W, Stockfleth E. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007 Dec;157 Suppl 2:34-40. doi: 10.1111/j.1365-2133.2007.08271.x.
- Individual participant dataSharing planned: No
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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.
Fernanda Visioli, PhD principal investigator
Federal University of Rio Grande do Sul
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imiquimod 5% gel, Imiquimod 0,05% gel and Imiquimod nanoencapsulated 0,05% gel in people with Actinic Cheilitis, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
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 4 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: stopped early, as of the sponsor's last update on 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated because of COVID19 pandemics.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response (time frame: 30 days after conclusion of treatment). The study lists 2 primary outcomes in all. 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 NCT04219358, which also lists 36 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 22 Nov 2022.