Comparison of Redermic, Rejuva-A and Combination of Both Redermic and Rejuva-A in Subjects With Signs of Aging

Study Overview
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Brief Summary
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Facial skin aging is a complex process combining factors such as sun exposure, smoking and those that are believed to be inherited. Changes in the skin over time including decreased thickness result in skin atrophy, wrinkling, sagging, yellowness and changes in pigmentation. Redermic is a cosmetic cream that has been evaluated clinically but not in comparison to tretinoin nor in combination with tretinoin. There is no data on the safety and efficacy of Redermic as compared to topical tretinoin. Rejuva is a cream currently approved by Health Canada for the treatment of photodamaged skin. It contains 0.025% tretinoin one of the most widely studied topical product for skin aging. Studies have shown that topical tretinoin increases collagen synthesis and epidermal thickness thereby improving the appearance of skin aging. The efficacy of Rejuva combined with another topical cosmetic cream such as Redermic in the treatment of skin aging is unknown. One hundred and twenty (120) subjects with signs of skin aging participated in this single-blind study to evaluate the efficacy and tolerance of Redermic versus Rejuva-A™ (0.025% tretinoin) and Redermic in combination with Rejuva-A™ (0.025% tretinoin).

Detailed Description
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Facial skin aging is a complex and multifactorial process combining extrinsic and intrinsic factors. Major extrinsic factors include sun exposure and smoking while intrinsic factors are believed to be genetically programmed. Changes in the dermis are responsible for many of the important clinical changes associated with skin aging. With age there is a decrease in the number of fibroblasts and a decrease in their ability to synthesize collagen which results in a decrease in collagen I and II. This is coupled with an increase in matrix metalloproteinases activity. Skin biopsies from elderly volunteers show changes in collagen bundles which become fragmented and disorganized as well as in elastin fibers which are decreased. Changes also occur in the epidermis including a decrease in epidermal thickness and a change in the morphology of keratinocytes of the basal layer. Clinically these changes result in skin atrophy, increased skin laxity, wrinkling, sagging, yellowness and changes in pigmentation. Redermic is a cosmetic cream containing vitamin C and madecassoside. A preliminary 20 subject split face study has shown that this product was well tolerated and could improve signs of skin aging. To evaluate changes in skin aging this study used a clinical evaluation of the face, skin hydration, the fringe technique, skin biopsies and skin elasticity measurements. The investigators did not perform transepidermal water loss (TEWL), facial skin evaluation using a photonumeric guideline, evaluation of photoaging by panel of blinded dermatologists or skin replica evaluations. There is no data on the combination of Redermic with tretinoin or on the safety and efficacy of Redermic as compared to topical tretinoin. Rejuva is a cream currently approved by Health Canada for the treatment of photodamaged skin. It contains 0.025% tretinoin one of the most widely studied topical product for skin aging. Studies have shown that topical tretinoin increases collagen synthesis and epidermal thickness thereby improving the appearance of skin aging. The efficacy of Rejuva combined with another topical cosmetic cream such as Redermic in the treatment of skin aging is unknown. The main objective of this single-blind study was to assess efficacy of the anti aging effect and the tolerance of Redermic alone compared to Rejuva-A™ (0.025% tretinoin) alone or in combination with Rejuva-A™ (0.025% tretinoin). One hundred and twenty (120) subjects with signs of skin aging participated in this single-blind study to evaluate the efficacy and tolerance of Redermic versus Rejuva-A™ (0.025% tretinoin) and Redermic in combination with Rejuva-A™ (0.025% tretinoin). Subjects were randomized (1:1:1) in three groups of forty (40), and were asked to apply study product to the face (except to eyelids, nostrils and other mucous membranes) for 24 weeks.

Official Title
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Single Blind Study to Evaluate the Tolerance and Effectiveness of Redermic Versus Rejuva-A™ (0.025% Tretinoin) and Redermic in Combination With Rejuva-A™ (0.025% Tretinoin) Under Normal Conditions in Subjects With Signs of Aging

Conditions
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Skin Aging

Intervention / Treatment
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* Other: Redermic
* Drug: Tretinoin (Rejuva-A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are female, between 45 and 55 years of age. Females of childbearing potential have had a negative urine pregnancy test prior to randomization. Subjects are willing to use adequate contraceptive method or are surgically sterile (including tubal ligation), post-menopausal, abstinent or with a same-sex partner. Adequate means of contraception include; intra-uterine device (IUD) in use for 30 days before Day 0, barrier methods and spermicide in use at least 14 days before Day 0 or oral contraceptive in use for at least 30 days before Day 0. Subjects are willing to avoid prolonged exposure to UV radiation for the duration of the study. Subjects are capable of giving written informed consent. Subjects have changes associated with facial skin aging/photodamaged skin. Exclusion Criteria: Subjects are male. Subjects are pregnant or lactating. Subjects have a known allergy to Redermic, Rejuva-A™ or to any component of the tested products. Subjects have made use of tretinoin, adapalene, tazarotene or other topical medications for the treatment of facial skin aging during the 12 weeks preceding Day 0. Subjects have applied topical alpha hydroxyl acids within 28 days of Day 0. Subjects have used or plan to use systemic corticosteroids within 28 days of Day 0 or during the study. Subjects have made use of a non-medication topical product directed at improving skin aging during the 28 days preceding Day 0. Subjects have a hypersensitivity to any retinoids. Subjects have a history of alcohol or drug abuse in the past year. Subjects are participating in another interventional study. Subjects have had a previous intense pulsed light treatment to the face. Subjects have had a previous laser treatment to the face directed at improving skin aging. Subjects have the presence of skin diseases such as psoriasis or dermatitis on the face that could interfere with study evaluations. Planned or unavoidable exposure to intense ultraviolet (UV) radiation during the study (such as sun tanning salons, vacations in a sunny climate or outdoor worker). Subjects have had a botulinum toxin A injection treatment on the face within 2 years of Day 0 or plan to receive this treatment during the study. Subjects have had a filler injection (collagen, hyaluronic acid, etc..) on the face within 2 years of Day 0 or plan to receive this treatment during the study.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Redermic<br>Cream was applied twice a day every day, morning and evening for 24 weeks. | Other: Redermic<br>* Cosmetic cream formulation 609637 43.<br>* Other names: vitamin C;|
| Active Comparator: Rejuva-A<br>Week 1, Rejuva-A cream was applied to face in the evening twice a week. Weeks 2 & 3, Rejuva-A cream was applied to the face in the evening three times a week. Weeks 4-24, Rejuva-A cream was applied to the face in the evening every other day. In cases of intolerance, returned to the previous dosage and remained there until the end of study. Hydrating cream was applied to the face in the morning every day for 24 weeks. | Drug: Tretinoin (Rejuva-A)<br>* Tretinoin 0.025% cream.<br>* Other names: Rejuva-A;|
| Active Comparator: Combination of Redermic and Rejuva-A<br>Week 1, Rejuva-A cream was applied to face in the evening twice a week. Weeks 2 & 3, Rejuva-A cream was applied to the face in the evening three times a week. Weeks 4-24, Rejuva-A cream was applied to the face in the evening every other day. In cases of intolerance, returned to the previous dosage and remained there until the end of study. Redermic was applied every evening when Rejuva-A™ was not applied, as well as every morning. | Other: Redermic<br>* Cosmetic cream formulation 609637 43.<br>* Other names: vitamin C;Drug: Tretinoin (Rejuva-A)<br>* Tretinoin 0.025% cream.<br>* Other names: Rejuva-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Aging Measured With the Photonumeric Scale. | Scoring was accomplished by matching each part of the face (forehead, glabella, corners of the mouth, nasal labial fold, crow's feet, below eyes and upper lip) to photographs in the scales and reporting the appropriate number in the tables. All individual scores were added to obtain the total score (Less signs of skin aging = 0, more signs of skin aging = 41.6). | 12, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Photographic Evaluation by a Panel of Blinded Dermatologists. | A blinded panel of two dermatologists had to identify independently which of the two photographs had an improvement or if there was no noticeable difference between them. The two photographs of each subject were randomized to keep the blind. When the Week 24 photograph was selected as the one showing an improvement, it was scored by the statistician as improvement. When the Day 0 photograph was selected as the one showing an improvement, it was scored by the statistician as worsening. When there was no noticeable difference between the photographs, it was scored as stable. | 24 weeks | 
| Trans-epidermal Water Loss (TEWL). | Trans Epidermal Water Loss (TEWL) was measured with a DermaLab device (Cortex Technology, Denmark) equipped with a TEWL probe. Measurements were performed with the subject lying down on the back in a room with controlled temperature (20°C +/-2) and relative humidity (45% +/- 15%). All measurements were performed at least 30 minutes after the subject was transferred into this room. The measurements were performed on the cheek. Care was taken to use the same cheek for each subject throughout the study. | 12, 24 weeks | 
| Skin Hydration (Conductance) | Skin hydration was measured with a DermaLab device (Cortex Technology, Denmark) equipped with a skin hydration probe. Measurements were performed in a room with controlled temperature (20°C +/-2) and humidity (45% +/- 15%). All measurements were performed at least 30 minutes after the subject had been transferred into this room. Care was taken to use the same cheek for each subject throughout the study. Higher values indicate greater hydration. | 12, 24 weeks | 
| Skin Elasticity. | Skin elasticity was measured with a DermaLab device (Cortex Technology, Denmark) equipped with a skin elasticity probe. Pressure required to raise the skin 1mm was recorded. Measurements were performed on the upper cheeks and care was taken to use the same location for all measurements. Final measurements were the average of left and right cheeks. When the product is a moisturizer, lower pressures are indicative of efficacy. | 12, 24 weeks | 
| Area Ratio - Analysis of Skin Replicas of Crow's Feet. | An illuminator is used to cross illuminate the specimen (silicone mold replicas) perpendicular to the major lines which accentuate the surface details. The resulting image which consists of a series of shadows that directly correspond to the pattern of wrinkles is digitized for analysis. One can measure changes in skin surface topography by selecting an area range (shadow size) that allows one to directly determine the projected area of the shadowed region associated with the wrinkles and major lines. The Area Ratio is the area of the shadows. The higher the ratio, the greater the wrinkling. | 24 weeks | 
| Clinical Skin Evaluation. | A clinical skin evaluation of the face was performed by a dermatologist using 8 scales (skin hydration, radiance, roughness, spots, laxity, skin tone homogeneity, softness, relief (variations in depth)). The individual scores were totalled (worst = 0, best = 47) and the total score was used for analyses. | 12, 24 weeks | 
| Sensitivity of the Face Evaluated by Subject. | Sensitivity of the entire face evaluated by the subject was performed using 4 different 10 cm visual analog scales (pruritus, tingling, burning, tightness). Each score was analysed separately. Each score is from 0 = absent to 10 important. | 12, 24 weeks | 
| Facial Skin Self-evaluation. | A visual analog scale of 13 evaluations were performed by the subject. Scale is from 1 - 10 for each evaluation individually evaluated. 0 = absent, 10 = important. | 12, 24 weeks | 
| Tolerance Evaluated by Investigator. | Tolerance was studied by evaluating scaling, dryness, erythema and burning/itching sensation on a 5-point scale. Scaling, Dryness and Erythema Evaluations - None (0) - Very Severe = (4) Burning and Itching Evaluation Scale None (0) = Normal, no discomfort Mild (1) = Slight discomfort that is not bothersome Moderate (2) = Discomfort that is somewhat bothersome Marked (3) = Discomfort that is bothersome and that occasionally interferes with normal daily activities Severe (4) = Continuous discomfort that interferes with normal daily activities | 12, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin, Aging, Rejuva-a, Redermic