Novel Compositions for Treating or Preventing Dermal Disorders

Study Overview
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Brief Summary
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This trial examines the impact of a topical formulation of rapamycin on dermal thickness and senescence.

Detailed Description
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Aging of the skin is the most prominent feature of the aging process, being caused by multiple factors such as intrinsic aging process and UV light exposure. Dermal atrophy, also called skin atrophy or atrophy, is a disorder manifesting thinning or depression of skin due to reduction of underlying tissue. Dermal atrophy is a major clinical problem in the elderly population. Loss of dermal integrity leads to increased fragility of the skin and precludes the use of intravenous lines in many cases. Skin tears are a significant concern in elderly individuals directly related to dermal atrophy. Impairment in wound healing is an important clinical sequelae of reduced dermal integrity leading to an increase in the number of the infections and complications following injury. Seborrheic keratosis, which comprise focal areas of epidermal thickening, can occur, possibly representing a response to damage. It has been estimated that 100% of individuals over 50 years of age harbor at least one of these lesion. There is not treatment for dermal atrophy and seborrheic keritoses require excision if they become large enough to cause discomfort or distress. Therefore, there is a need to develop novel compositions and methods for treating or preventing certain age-related dermal conditions. Rapamycin is an FDA approved drug that has been in clinical use for over 15 years. Systemic application of rapamycin has been a central part of immuno suppressive therapy for transplant patients in combination with other immuno suppressants. The safety record for systemic use of rapamycin is excellent and few side effects are associated with extended use.

Official Title
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Novel Compositions for Treating or Preventing Dermal Disorders

Conditions
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Dermal Atrophy

Intervention / Treatment
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* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults Exclusion Criteria: Individuals with any chronic disease will be excluded from the study including those with the following conditions: Diabetes Any type of Malignancy Severe coronary artery disease HIV infection Hepatitis C or B Any sign of skin disorder or disease aside from normal aging, dermal atrophy, or seborrheic keratoses. Premenopausal women will be excluded Patients taking the following medications will be excluded: Cyclosporin Calcium channel blockers: diltiazem, verapamil Antifungal agents e.g. clotrimazole, fluconazole, itraconazole Antibiotics: clarithromycin, erythromycin, rifampicin Anticonvulsants: carbamazepine, phenobarbitone, phenytoin Antinausea drugs e.g. metoclopramide Other drugs e.g. danazol, protease inhibitors (e.g. for HIV and hepatitis C including ritonavir, indinavir, boceprevir, and telaprevir) Grapefruit juice St John's wort (Hypericum perforatum, hypericin)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 100 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will apply lotions containing either rapamycin or vehicle to 2 distinct areas of sun exposed skin.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin<br>Rapamycin | Drug: Rapamycin<br>* topical formulation<br>* Other names: sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermal thickness | dermal thickness as assessed by direct measurement | 6-8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression | immunohistochemistry and gene expression analysis | 6-8 months | 
| Seborrheic Keratosis | clinical severity will be assess using a 1-5 rating scale of severity. Lesions will be evaluated for their progression over the treatment period relative to the known course of growth for Seborrheic Keratoses. | 6-8 months |