Topical Application of Imiquimod Gel at Different Concentrations in Actinic Cheilitis

• Sponsor: Hospital de Clinicas de Porto Alegre (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT04219358
• Collaborator: Federal University of Rio Grande do Sul (Other)
• Enrollment: 172
• Locations: 2
• Arms: 4
• Anticipated Duration (Months): 21.3
• Patients Per Site: 86
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Actinic Cheilitis	Drug: Vehicle Gel Base; Drug: Imiquimod 5% gel; Drug: Imiquimod 0,05% gel; Drug: Imiquimod nanoencapsulated 0,05% gel; Drug: Lip sunscreen 30 Sun Protector Factor (SPF); Drug: Dexpanthenol	Phase 2/Phase 3

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

• Study Type: Interventional
• Anticipated Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: A pharmacist, who will not have contact with the study subjects at any time, will prepare the hydrogels in transparent sealed syringes, which will be numerically coded and two spreadsheets with the codes will be generated and placed in sealed brown envelopes. One envelope will be held by the pharmacist and the other envelope will be placed in a safe place. Participants will not know which medication they received until the end of the experimental phase. The vehicle gel is identical in appearance to those containing imiquimod. If for any reason the information on which treatment has been allocated is required, the external assistant will take all possible measures to ensure that the masking is not broken. The examiners who will perform the treatment and clinical evaluation will be blinded to the experimental group. Primary outcome measure is based on clinical evaluation of lesions by photographs. The images will be coded in order to achieve blindness of outcome assessors.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 23, 2019
• Anticipated Primary Completion Date: Dec 31, 2020
• Anticipated Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Placebo & Standard Treatment	Drug: Vehicle Gel Base; 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.; Drug: 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: Dexpanthenol; 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.
Experimental: Imiquimod 5% & Standard Treatment	Drug: Imiquimod 5% gel; 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%.; Drug: 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: Dexpanthenol; 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.
Experimental: Imiquimod 0.05% & Standard Treatment	Drug: Imiquimod 0,05% gel; 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.; Drug: 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: Dexpanthenol; 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.
Experimental: Imiquimod nanoencapsulated 0.05% & Standard Treatment	Drug: Imiquimod nanoencapsulated 0,05% gel; 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%; Drug: 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: Dexpanthenol; 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.

Outcome Measures

Primary Outcome Measures

1. Clinical Response [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.

2. Clinical Response [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.

Secondary Outcome Measures

1. General Satisfaction about the medication: Visual Analogue Scale (VAS) [VAS scale will be generated at 14 days after beginning of the treatment.]

   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.

2. General Satisfaction about the medication: Visual Analogue Scale (VAS) [VAS scale will be generated at 28 days after beginning of the treatment.]

   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.

3. General Satisfaction about the medication: Visual Analogue Scale (VAS) [VAS scale will be generated at 60 days after beginning of the treatment.]

   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.

4. General Satisfaction about the medication: Visual Analogue Scale (VAS) [VAS scale will be generated at 210 days after beginning of the treatment.]

   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.

5. Adverse Events Severity [The adverse events questionnaire is applied in 14 days after beginning of the treatment.]

   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.

6. Adverse Events Severity [The adverse events questionnaire is applied in 28 days after beginning of the treatment.]

   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.

7. Adverse Events Severity [The adverse events questionnaire is applied in 60 days after beginning of the treatment.]

   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.

8. Adverse Events Severity [The adverse events questionnaire is applied in 210 days after beginning of the treatment.]

   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.

9. Maturation epithelial pattern [Maturation epithelial pattern analysis will be performed at 28 days after beginning of the treatment.]

   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.

10. Maturation epithelial pattern [Maturation epithelial pattern analysis will be performed at 60 days after beginning of the treatment.]

    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.

11. Maturation epithelial pattern [Maturation epithelial pattern analysis will be performed at 210 days after beginning of the treatment.]

    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.

12. Cell proliferation - mAgNOR [mAgNOR analysis will be performed at 28 days after beginning of the treatment.]

    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.

13. Cell proliferation - mAgNOR [mAgNOR analysis will be performed at 60 days after beginning of the treatment.]

    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.

14. Cell proliferation - mAgNOR [mAgNOR analysis will be performed at 210 days after beginning of the treatment.]

    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.

15. Cell proliferation - pAgNOR [pAgNOR analysis will be performed at 28 days after beginning of the treatment.]

    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.

16. Cell proliferation - pAgNOR [pAgNOR analysis will be performed at 60 days after beginning of the treatment.]

    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.

17. Cell proliferation - pAgNOR [pAgNOR analysis will be performed at 210 days after beginning of the treatment.]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Individuals with clinical and histopathological diagnosis of actinic cheilitis;

• No previous lip treatment with Imiquimod.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90040-060
2	School of Dentistry - Universidade Federal do Rio Grande do Sul	Porto Alegre	Rio Grande Do Sul	Brazil	90040-060

Sponsors and Collaborators

• Hospital de Clinicas de Porto Alegre
• Federal University of Rio Grande do Sul

Investigators

• Principal Investigator: Fernanda Visioli, PhD, Federal University of Rio Grande do Sul

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Hospital de Clinicas de Porto Alegre
• ClinicalTrials.gov Identifier: NCT04219358
• Other Study ID Numbers: 2018-0656
• First Posted: Jan 7, 2020
• Last Update Posted: Jan 7, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Hospital de Clinicas de Porto Alegre: imiquimod; nanoencapsulation
• Additional relevant MeSH terms: Cheilitis; Imiquimod; Sunscreening Agents

Study Results

No Results Posted as of Jan 7, 2020