Menthol for PDT Pain Relief

Study Overview
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Brief Summary
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Topical photodynamic therapy (PDT) is widely used to treat superficial non-melanoma skin cancer (NMSC) and dysplasia, notably actinic keratosis and may also be effective in a range of other dermatological conditions. A major limitation of PDT is pain during irradiation. A lack of knowledge of the mechanism of PDT-induced pain has limited the development of effective approaches for prevention or relief of this adverse effect. The investigators have investigated the possible efficacy of menthol for PDT pain ex vivo and will now study this in a clinical trial. This proposal describes the prospective randomised double blind, placebo controlled clinical trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.

Detailed Description
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This proposal describes the prospective randomised double blind, placebo controlled clinical trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee. This will be undertaken by comparison of 5% menthol in aqueous cream with aqueous cream as placebo and the primary outcome measures will be pain recorded on a visual analogue scale (VAS) during and up to 24 h after PDT. Secondary outcomes are phototoxicity, assessed by a semi-quantitative scoring system immediately after PDT, fluorescence assessed routinely after cream application and before irradiation and outcome based on clinical assessment three months after PDT and patient evaluation. Patients will be involved in the study from the first visit for PDT until the three-month assessment visit after PDT. Data analysis will be undertaken using within-subject paired analyses as patients act as their own control. Information from this study will inform investigators as to whether topical menthol should be routinely incorporated into PDT treatment regimens in order to reduce pain and increase tolerance of treatment. The information will also provide additional information as to the mechanisms of PDT-induced pain and its possible prevention and/or relief.

Official Title
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A Randomised Double Blind, Placebo Controlled Study of the Efficacy of Topical Menthol for Pain Relief During Topical Photodynamic Therapy

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Menthol
* Drug: Aqueous Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: Adults >18 years. Target population is men or women ≥50 years (only post-menopausal women) Presence of actinic keratoses (AK) on the face and scalp involving both right and left comparable sites. Free of significant physical abnormalities (e.g. tattoos, dermatoses) in the potential treatment area that may cause difficulty with examination or final evaluation. Able to understand and adhere to protocol requirements. Exclusion Criteria: Unable to give written informed consent. Allergy to menthol, aqueous cream or excipients Participation in a drug trial or other interventional study within 30 days of recruitment to this study Pre-menopausal women, pregnancy, breast feeding, planning to conceive Chronic pain

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Menthol<br>5% menthol in aqueous cream (Dermacool Forte) | Drug: Menthol<br>* Topical menthol in aqueous cream<br>* Other names: 5% menthol in aqueous cream;|
| Placebo Comparator: Placebo<br>Aqueous cream | Drug: Aqueous Cream<br>* placebo<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain immediately after PDT assessed by VAS score | pain immediately after and at 3, 6 and 24 h after PDT assessed by VAS score | 24h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance: clear/partially clear/not clear - clinical assessment visually and by palpation | Clearance (CR), partial clearance (PR) or no clearance (NR) will be recorded on each side in each participant | 3 months after treatment | 
| Erythema (redness) (none/mild/moderate/severe) | Erythema grading (none/mild/moderate/severe) will be recorded on each side in each participant | Immediately after PDT | 
| fluorescence assessed as none/mild/moderate/strong using Wood's light examination | Fluorescence of each side in each participant will be recorded | Immediately before and after PDT | 
| patient preference - preferred right or left side or no preference | patient questionnaire completed at home and returned in SAE | 24h | 
| swelling | Swelling present or absent will be recorded on each side in each patient | immediately after PDT | 
| Exudation | Exudation present or absent will be recorded on each side in each patient | immediately after PDT | 
| urticaria | Urticaria present or absent will be recorded on each side in each patient | immediately after PDT |