A Trial of Polypodium Leucotomos in Preventing Skin Cancer and Its Precursors

Study Overview
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Brief Summary
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This proposal describes a pilot study to gather preliminary evidence of efficacy, tolerability and toxicity of oral PLE among a high-risk skin cancer population for the prevention of Actinic keratosis (AKs) and keratinocytes (KCs) to gain insight into optimal methods for recruitment, intervention development, data collection, and promoting protocol adherence prior to conducting a fully powered trial. The primary clinical outcome is AKs as measured by a clinical dermatologist, with skin cancer as a secondary clinical outcome. The investigators will also assess histologic markers of Ultra Violet (UV) damage, which have previously been shown to be reduced with oral PLE use in human studies, namely formation of UV-induced cyclo pyrimidine dimer positive cells and number of sunburn cells among epidermal keratinocytes. Results generated from this proposal will form the foundation of a fully powered clinical trial of the effect of PLE on the risk of AKs and KCs. The results may also provide information about this promising dietary supplement which may provide extra protection for a high-risk skin cancer population.

Detailed Description
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Polypodium leucotomos is a tropical fern, the extract of which has shown photoprotective effects in animal and human models, and is currently available as an over-the-counter dietary supplement. Polypodium leucotomos extract (PLE) has been shown in laboratory, animal, and clinical studies to serve as a potent antioxidant that helps mitigate UV-induced damage by scavenging free radicals and reactive oxygen species. Oral consumption of PLE in human studies has been shown to significantly reduce the number if UV-induced sunburn cells and DNA damage, and to inhibit photosensitization. Importantly, PLE appears to be exceptionally well-tolerated with no serious reported adverse side effects. PLE has been studied in numerous trials for many conditions, including skin diseases. Doses up to 1200 mg per day have been used in clinical studies, though doses for prevention of sun-damage are typically in the range of 480 mg per day. To date, no serious adverse effects have been clearly attributed to the use of PLE (this high tolerability is one of the reasons for the great interest in the clinical use of PLE). Oral consumption of other fern species, such as Polypodium vulgare, have been associated with low blood pressure and increased heart rate. On theoretical grounds, similar side effects may be possible with PLE.

Official Title
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A Pilot Trial of Polypodium Leucotomos in Preventing Skin Cancer and Its Precursors

Conditions
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Keratosis, Actinic, Keratosis, Skin Neoplasms

Intervention / Treatment
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* Drug: Heliocare with Fernblock PLE technology
* Other: Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be male or female and at least 18 years of age. Female patients must be of: Non-childbearing potential; Childbearing potential, provided negative urine pregnancy test and using effective contraception. Dermatologist-rendered diagnosis of AK in the past 2 years. Exclusion Criteria: History of >2 skin cancers in the past 5 years History of dementia Cardiovascular disease, defined as Blood Pressure (BP) <90/60 or Heart rate (HR) >110 in the past year or a history of myocardial infection Inflammatory bowel disease/irritable bowel syndrome Treatment with Fluorouracil, imiquimod, diclofenac, or photodynamic therapy in the past 8 weeks Intention to seek more aggressive AK therapy such as photodynamic therapy, laser surgery in next 12 months Serious psychological illness History of alcohol or drug abuse Any disease or condition which would interfere with study participation or unduly increase risk.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heliocare<br>240 mg administered orally daily | Drug: Heliocare with Fernblock PLE technology<br>* 240 mg taken orally daily over the course of 1 year<br>* Other names: Polypodium leucotomos extract capsules;|
| Placebo Comparator: Sugar pill<br>a sugar pill matching the Heliocare tablet in look and weight will be administered orally daily | Other: Sugar Pill<br>* A pill that appears similar to the supplement<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of new clinically visable AKs as measured by a full skin exam performed by a blinded, board certified dermatologist (Dr. Asgari). |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic presence of UV-induced cyclobutane pyrimidine dimer positive cells |  | one year | 
| Degree of solar elastosis assessed using Verhoeff stain on biopsy specimens obtained from punch biopsy |  | one year | 
| Counts of sunburnt cells in sun exposed skin |  | one year |