Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation
April 2018 | Volume 17 | Issue 4 | Original Article | 426 | Copyright © 2018
Amy Taub MD,a Vivian Bucay MD,b Gregory Keller MD,c Jay Williams PhD,c and Darius Mehregan MDd
aAdvanced Dermatology/Skinfo, Lincolnshire, IL; Northwestern University Medical School, Department of Dermatology, Chicago, IL bBucay Center for Dermatology and Aesthetics, San Antonio, TX cGregory Keller Plastic Surgery, Santa Barbara, CA dWayne State University, Monroe, MI
cells of the skin,19 defensins mobilize normally quiescent and relatively undamaged stem cells.20 The targeted and specific use of defensins to activate LGR6-positive stem cells may provide a safer and more effective and targeted approach to skin aging therapy. A six-week pilot study in which 22 human subjects applied a skin care regimen of synthetic α-defensin 5 and β-defensin 3 was reported in 2014 (Keller). The results showed a global improvement in wrinkles, pores, skin’s evenness, and a reduction in skin oil production. These encouraging results led to the present study, which evaluates an anti-aging skin care product containing alpha and beta defensins in 44 patients over 12 weeks.
Study Design Overview
Institutional Review Board approval was obtained for this study and the study was performed using Good Clinical Practice Guidelines21 as published by the U.S. Food and Drug Administration (FDA). This is an investigator-initiated study that was registered at clinicaltrials.gov prior to subject enrollment (#NCT02765763). All study participants who met inclusion criteria and were enrolled into the study were split into two groups: the study subjects of the full formula group (FFG) used treatment contained all active substances, a three-product group consisting of a serum, a cream, and a mask. The study subjects of the placebo group (PG) used only vehicle formulas (no active ingredients) in containers and a serum, cream, and mask that were otherwise identical to the FFG. Both the study subjects and their physicians were blinded in terms of the treatment groups (double-blinded study). The participants were assigned to groups by the research coordinator in a random fashion and without the investigator’s or participant’s knowledge (a randomized study). Subjects were evaluated at baseline, 6 weeks, and 12 weeks.
Forty-six female subjects participated in this study (15-16 participants per clinical site). Inclusion criteria included female gender, ages 40-75, any skin type, and anyone in good health who can freely participate voluntarily and agreed to potentially have a biopsy in the post-auricular area before and at either 6 weeks or 12 weeks after usage of the study materials. Exclusion criteria included current use of topical or systemic anti-aging therapy, a history of any acute or chronic disease that might interfere with or increase the risk of study participation, chronic skin allergies, history of skin cancer treated within the last 12 months, or insulin-depended diabetes. Also excluded were individuals who had undergone any of the following procedures: Botulinum toxin, lasers or tissue tightening devices, or other energy based devices used on the face or neck within 6 months before enrollment into the study and until study completion, injectable filler within 3 months before enrollment into the study and until study completion, poly-L-lactic acid or bovine collage with polymethylmethacrylate at any time prior to enrollment into the study and until study completion. Subjects underwent a 1-week washout period to remove all anti-aging skin care products, if any were utilized (antioxidants, retinol or retinoid, alpha hydroxy acid, peptides, growth factors). Participants were randomly assigned to the PG (15 participants, 4-5 per clinical site) or to the FFG (31 participants, 9-11 per clinical site). Clinical sites included: (Site 1) Advanced Dermatology, Lincolnshire and Glencoe, IL, (Site 2) Bucay Center for Dermatology and Aesthetics, San Antonio,TX, and (Site 3) Gregory Keller Facial Plastic Surgery, Santa Barbara, CA. The mean age of the subjects in both the FFG and PG was 60 years. In the FFG, the age range was 41-69 years, Fitzpatrick’s skin types I-V. In the PG, the age range was 45-71 years, Fitzpatrick’s skin types II-IV. Forty-six participants were recruited and 44 participants completed the study. There was one dropout from the FFG at Site 2 and one dropout from PG at Site 3, (neither were product-related).
A skin care regimen containing liposome-incorporated, synthetically produced biomimetic alpha-defensin 5 and beta-defensin 3, were tested in this study. The regimen (DefenAge®, Progenitor Biologics LLC, (a division of MediCell Technologies, Carlsbad, CA) included the 2-Minute Reveal Masque (mask applied once or twice weekly), 24/7 Barrier Balance Cream (cream applied BID), and 8-in-1 BioSerum (serum applied BID) either supplemented with the performance ingredients (FFG) or without the performance ingredients (vehicle only, PG). Placebo product was identical to full formula product in packaging. The lists of ingredients of full formula product and placebo products are shown in Table 1. The test products (in both FFG and PG) were applied directly on the face, postauricular, and neck skin for 12 weeks. All study subjects also washed these testing areas of the skin twice daily with Topix Non-Drying Gentle Cleanser Lotion (Ingredients: purified water, dea-lauryl sulfate, propylene glycol, cetyl alcohol, stearyl alcohol, hydroxyethylcellulose, methylparaben, propylparaben, methylchloroisothiazolinone, methylisothiazoilnone, FD&C Blue #1) and used Topix Elite Sunscreen SPF 30 (Ingredients: zinc oxide 17%, purified water, C12-15 alkyl benzoate, cyclomethicone, laurylmethicone copolyol, C13-14 isoparaffin, polyacrylamide, ceresin, dimethicone, green tea extract, phospholipids, ascorbyl palmitate, tocopheryl acetate, retintyl palmitate, Co-Q10, ascorbyl glucosamine, superoxide dismutase, laureth-7, sodium chloride, methylparaben, propylparaben, diazolidinyl urea) daily each morning after application of the testing regiment.
All 46 participants underwent medical imaging using the VISIA CA (Bucay), CR (Canfield, NJ;Taub), or the 3D LifeViz (QuantifiCare, France; Keller) along with evaluation of skin conditions