Green Tea and Ultraviolet Light-induced Skin Damage

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate whether topically applied constituents of green tea [caffeine or (-)-epigallocatechin gallate; EGCG] have a protective effect on skin exposed to ultraviolet light (UV).

Detailed Description
-----------------
The purpose of this study is to investigate if topically applied constituents of green tea [caffeine or (-) - epigallocatechin gallate; EGCG] have a protective effect on skin exposed to ultraviolet light (UV). In the double-blinded study all subjects will receive 311 nanometer UVB light at a dose that is 0.5-1.5X their individual minimal erythema dose (MED). One part of the experiment will involve applying a topical natural product (caffeine or EGCG) and placebo to bilateral symmetric sites. The natural product and the placebo will be applied immediately after and at 1/2 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours, 25 hours, and 27 hours after exposure to a 0.5-1.5 MED dose of UV light. Another part of the study involves performing skin biopsies. One will be done prior to UVB exposure, 2 will be done at 24 hours and 2 more will be done at 48 hours.

Official Title
-----------------
The Effects of Topically Applied Constituents of Green Tea on UV Induced Increase in p53 and Apoptotic Markers in the Skin of Human Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Green Tea
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subjects will be normal adult volunteers who are 18 to 65 years of age. Exclusion Criteria: Subjects who drink more than two cups of coffee, tea, or caffeinated soda/beverages per day. Subjects who are unable to get an erythemic response (i.e., a sunburn).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active drug<br>bilateral comparison of green tea constituent | Drug: Green Tea<br>* Green tea product (EGCG or caffeine) in vehicle will be applied immediately after and at sequential time points after exposure of a 5x5-cm area of skin to a dose of UVB that is 0.5-2 times the subject's minimal erythema dose (MED)<br>|
| Placebo Comparator: placebo<br>bilateral comparison of placebo vehicle | Drug: Placebo<br>* Placebo (vehicle alone) will be applied immediately after and at sequential time points after exposure of a 5x5-cm area of skin to a dose of UVB that is 0.5-2 times the subject's minimal erythema dose (MED)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in UVB-Induced Active Caspase-3-Positive Keratinocytes by Green Tea Compounds | The mean change in number of active caspase-3+ apoptotic keratinocytes between 0- and 48-hour time points was calculated for skin biopsy samples of subjects who had been exposed to UVB on symmetrical right and left test sites which were then randomized to receive active test substance (EGCG or caffeine) or placebo (vehicle) at sequential time points after UVB exposure. | 48 hrs | 
| Change in UVB-Induced Apoptotic Sunburn Cells by Green Tea Compounds | The mean change in number of apoptotic sunburn cells between 0- and 48-hour time points was calculated for skin biopsy samples of subjects who had been exposed to UVB on symmetrical right and left test sites which were then randomized to receive active test substance (EGCG or caffeine) or placebo (vehicle) at sequential time points after UVB exposure. | 48 hr | 
| Effect of Topical Applications of 4-6% Caffeine on UVB-Induced Increases in Apoptotic Sunburn Cells | The percentage of apoptotic sunburn cells was identified in the 48-hr time point skin biopsy samples of subjects who had been exposed to UVB on symmetrical right and left test sites which were then randomized to receive 4-6% caffeine in cream vehicle or placebo (cream vehicle) at sequential time points after UVB exposure. | 48 hr | 
| Effect of Topical Applications of 4-6% Caffeine on UVB-Induced Increases in Caspase-3-Positive Cells | The percentage of caspase-3-positive cells was identified in the 48-hr time point skin biopsy samples of subjects who had been exposed to UVB on symmetrical right and left test sites which were then randomized to receive 4-6% caffeine in cream vehicle or placebo (cream vehicle) at sequential time points after UVB exposure. | 48 hr | 
| Effect of Topical Applications of 4-6% Caffeine on UVB-Induced Increases in Phospho-p53 (Ser15) Positive Cells | The percentage of phospho-p53 (Ser15) positive cells was identified in the 48-hr time point skin biopsy samples of subjects who had been exposed to UVB on symmetrical right and left test sites which were then randomized to receive 4-6% caffeine in cream vehicle or placebo (cream vehicle) at sequential time points after UVB exposure. | 48 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Green Tea Compounds on UVB-Induced Erythema | Erythema of the right and left test sites was scored on a scale of 0-3 (0 = no evidence [no erythema]; 1 = mild [pink or light red color]; 2 = moderate [red color]; 3 = severe [very red or dark color]) including half-integer grading. Scoring was performed immediately after UVB exposure and at sequential time points thereafter. The mean scores at 48 hr were calculated. | 48 hrs | 
| Effect of 4-6% Caffeine on UVB-Induced Erythema | Erythema of the right and left test sites was scored on a scale of 0-3 (0 = no evidence [no erythema]; 1 = mild [pink or light red color]; 2 = moderate [red color]; 3 = severe [very red or dark color]) including half-integer grading. Scoring was performed immediately after UVB exposure and at sequential time points thereafter. The erythema scores at 6, 8, and 24 hr post-UVB were averaged. | 24 hr | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Normal volunteer study