Double-Blind Study Determining the Efficacy of CannaXR in Decreasing UVA Premutagenic and Photoaging Markers

Study Overview
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Brief Summary
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Ultraviolet light A (UVA) causes oxidization of guanine to mutagenic 8-Oxoguanine (8-OxoG) and the most frequent and best characterized mutation in mitochondrial DNA (mtDNA), a deletion of 4,977 base pairs, called the common deletion, a marker of photoaging.

Detailed Description
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Evaluations & Schedule: Clinical phase: The study of each subject will last 4-5 weeks, with 7 visits (Screening visit 1, Baseline visit 2, Follow up visit 3, Follow up visit 4, Follow up visit 5 and Follow up/Final Visit 6). Screening Visit: Subjects will read and be explained the informed consent. Subjects who agree to participate will sign the informed consent and a copy will be given to them. Exclusion/inclusion criteria will be reviewed. Subjects will be informed that the left arm will be photographed at visits 1 and 3 and both hip/buttock areas at each visit. A urine pregnancy test will be done on baseline (Visit 1, day 0) and final visit 6. Visit 2, Baseline (day 0): Baseline visit will be done no more than 21 days after the screening visit and may be done on the same day as the screening visit. Each subject will be instructed not to change any of his/her photoprotection practices during the duration of the study, including time spent outdoors each weekday and weekend day, with special attention between the hours of 10 AM and 4PM, and sunscreen use and parts of their body where they apply it. The subject's left volar forearm will be exposed to 10, 15, 20, 25, 30, and 35 J/cm2 doses of ultraviolet A light, through a UVA opaque fenestrated adhesive patch placed, 2 cm distally from antecubital fossa. Appropriate UVA opaque shields will be used to protect surrounding untreated areas. In double-blinded fashion, subjects will receive sufficient CANNAXR (extended release) cream (CANNAXR pods filled with CBD) and VEHICLE cream (cream with empty CANNAXR pods without CBD) in pump containers, marked right or left, with detailed application instructions and a template for each cream to be applied to specified 50 cm2 areas of either the left and right, hip/buttock skin daily in the morning and evening for 2 weeks, starting the next morning. Visit 3 (Day 1): MED-A (minimal erythema dose for UVA) will be determined by evaluating skin exposed the prior day to the different UVA doses. MED-A will be defined as the dose that produced just perceptible erythema. Visit 4 (Day 14) Subjects will be asked about adverse events (predicted or unpredicted, local or systemic) since the last visit. Within the treated areas of the right and left hip/buttock, skin will be treated through fenestrated adhesive UVA-opaque patches as follows: Window #1- no UVA dose, and Window #2 - 3x the subjects UVA-MED (determined on Day 1). Visit 5 (Day 15): Subjects will be asked about adverse events (predicted or unpredicted, local or systemic) since the last visit. Local anesthesia (lidocaine 2% with epinephrine) will be injected and a 4mm punch biopsy will be performed of the skin of each hip/buttock within the templated Windows #1 and #2, as well as at a site 10 cm from the treated area of the left hip/buttock. One or two 5-0 sutures will be placed to appose the skin edges at each of the biopsied sites. Skin biopsy specimens will be divided in half and placed in labelled containers containing appropriate media for 8-oxo-dG (8-oxo deoxyguanosine), common deletion, histochemical and immunochemical studies. Specimens will be shipped to Dr. Adam Friedman for analyses. Supplies and wound care instructions will be given. Visit 6, Final (Day 22-30): Subjects will be asked about adverse events (predicted or unpredicted, local or systemic) since the last visit and all sutures placed at Visit 5 will be removed. A urine pregnancy test will be done. Notes: If an erythematous response after UVA light exposure is symptomatic (burning and tenderness), subjects will be allowed to use twice a day hydrocortisone 1%, over the counter cream, to treat the area. We will provide the cream at the office. Visit 3 has to occur 20-28 hours after baseline visit 2. Visit 5 has to occur 20-28 hours after Visit 4.

Official Title
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Double-Blind Study Determining the Efficacy of CannaXR in Decreasing UVA Premutagenic and Photoaging Markers

Conditions
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Photoaging

Intervention / Treatment
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* Device: In a double-blinded fashion, 250 mg CANNAXR cream
* Device: Topical VEHICLE cream


Participation Criteria
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Eligibility Criteria
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Population: Inclusion criteria: Healthy subjects 22-65 years of age Fitzpatrick skin types II and III Exclusion criteria: Pregnancy Personal history of skin cancer History of abnormal photosensitivity Tobacco smoker History or being exposed to other forms of radiation (other than sunlight) Using any drug/medication that might alter the response of skin to UVA irradiation Unable to undergo skin biopsies History of abnormal scarring History of exposure to the treated areas with external beam X-ray or non-solar UV light irradiation

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Study Design: Prospective, double-blind, vehicle-controlled pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Loaded CANNAXR<br>In a double-blinded fashion, 250 mg CANNAXR cream and 250 mg VEHICLE cream will be randomized for application to a delineated 50 cm2 area of either the left or right, hip/buttocks skin twice daily for 2 weeks. In a double-blinded fashion, 250 mg CANNAXR cream and 250 mg VEHICLE cream will be randomized for application to a delineated 50 cm2 area of either the left or right, hip/buttocks skin twice daily for 2 weeks. | Device: In a double-blinded fashion, 250 mg CANNAXR cream<br>* Determining the Efficacy of topically applied CANNAXR cream in Decreasing UVA Premutagenic and Photoaging markers 8-oxo-dG and the common deletion. 250 mg TOPICAL CBD CANNAXR Cream will be randomized for application to a delineated 50 cm2 area of either the left or right, hip/buttocks skin twice daily for 2 weeks<br>* Other names: TOPICAL CBD CANNAXR Cream;Device: Topical VEHICLE cream<br>* Determining the Efficacy of topically applied VEHICLE cream in Decreasing UVA Premutagenic and Photoaging markers 8-oxo-dG and the common deletion. 250 mg VEHICLE cream will be randomized for application to a delineated 50 cm2 area of either the left or right, hip/buttocks skin twice daily for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Title: Double-Blind Study to measure and compare the Mean Percent Reduction UVA induced premutagenic and photoaging markers 8-oxo-dG and the common deletion in 20 subjects treated with CANNAXR and Vehicle and exposed to 3X their individual MED-UVA | Determining the Efficacy of topically applied CANNAXR cream vs vehicle cream in decreasing UVA induced Premutagenic and Photoaging markers 8-oxo-dG and the common deletion in 20 subjects exposed to 3X their individual MED-UVA: Comparison of mean percent reduction in UVA induced 8-Oxo-DG and common deletion in CANNAXR and Vehicle treated skin and exposed to 3X MED-UVA | 2 weeks |