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Topical Application of Imiquimod Gel at Different Concentrations in Actinic Cheilitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04219358
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Federal University of Rio Grande do Sul
Information provided by (Responsible Party):
Hospital de Clinicas de Porto Alegre

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 23, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Imiquimod

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.





Primary Outcome Measures :
  1. 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.


  2. 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.



Secondary Outcome Measures :
  1. General Satisfaction about the medication: Visual Analogue Scale (VAS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04219358


Contacts
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Contact: Eduardo L da Silva, DDS 55 51 3308 5025 ext 5011 edu.liberato.s@gmail.com
Contact: Fernanda Visioli, PhD 55 51 3308 5025 ext 5011 fvisioli@hcpa.edu.br

Locations
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Brazil
Hospital de Clínicas de Porto Alegre Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90040-060
Contact: Fernanda Visioli, PhD    55 51 3308 5011 ext 5011    fvisioli@hcpa.edu.br   
Contact: Eduardo L da Silva, DDS    55 51 3308 5011 ext 5011    edu.liberato.s@gmail.com   
School of Dentistry - Universidade Federal do Rio Grande do Sul Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90040-060
Contact: Fernanda Visioli, PhD    55 51 3308 5011 ext 5011    fvisioli@hcpa.edu.br   
Contact: Eduardo L da Silva, DDS    55 51 3308 5011    edu.liberato.s@gmail.com   
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Federal University of Rio Grande do Sul
Investigators
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Principal Investigator: Fernanda Visioli, PhD Federal University of Rio Grande do Sul
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: January 7, 2020    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Cheilitis
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Imiquimod
Sunscreening Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents
Dermatologic Agents