INTRODUCTION
In the development of a topical body skin treatment (SkinMedica Firm & Tone Lotion for Body [FTB]; Allergan Aesthetics, an AbbVie Company, Irvine, CA) to address age-related skin problems, a key focus has been the identification of pathways important to body skin health and rejuvenation that are responsive to modulation by selected botanical preparations.1 FTB was formulated to target key pathways that contribute to overall skin quality, including improved dermal extracellular matrix integrity, enhanced lymphatic drainage, cellular clearance and recycling, and adipocyte metabolism.1 FTB was originally conceived and shown to be tolerable and effective in improving body skin quality when applied to the upper arms and thighs.2 However, the active botanicals identified via this rational treatment approach might also target pathways capable of further improving skin tone evenness, skin firmness, and other aesthetic attributes overlying the skin following noninvasive body contouring (NIBC) procedures.1
NIBC techniques that target subcutaneous fat include cryolipolysis,3 high-intensity focused ultrasound,4 low-level near-infrared laser lipolysis,5 and combined high-intensity focused electromagnetic field and radiofrequency lipolysis.6,7 The use of NIBC techniques continues to grow. Worldwide, an estimated 560,464 nonsurgical fat reduction procedures were performed in 2020, an increase of 29% versus 2016.8 In the United States, over 1 million body sculpting procedures were performed in 2019.9 Approximately 26% (257,868) were cryolipolysis, representing a more than 3-fold increase since 2012.9,10 The popularity of NIBC stems from its ability to deliver fat reduction noninvasively without the need for anesthesia and a faster recovery time compared with invasive liposuction.11,12
Cryolipolysis is the process by which controlled cooling extracts heat from subcutaneous tissue to induce selective adipocyte cell death, thereby reducing the thickness of the subcutaneous fat layer.13-16 There is also clinical evidence of skin tightening and texture improvement in cryolipolysis-treated areas, along with immunohistochemical evidence that neocollagenesis may play a role.16-19 It is thus also reasonable to assume that further enhancement of the skin appearance can be achieved by applying topical treatments that target multiple relevant processes following cryolipolysis.1,20
To characterize the effect of FTB as an adjunct to NIBC procedures, we conducted a pilot, open-label, single-site study of subjects who had pre-elected to undergo cryolipolysis on the inner thighs, back/bra fat, and/or submental areas. The objective of the study was to evaluate the safety and efficacy of FTB as an adjunct to NIBC, especially concerning post-procedure improvements in body skin firmness and texture.
NIBC techniques that target subcutaneous fat include cryolipolysis,3 high-intensity focused ultrasound,4 low-level near-infrared laser lipolysis,5 and combined high-intensity focused electromagnetic field and radiofrequency lipolysis.6,7 The use of NIBC techniques continues to grow. Worldwide, an estimated 560,464 nonsurgical fat reduction procedures were performed in 2020, an increase of 29% versus 2016.8 In the United States, over 1 million body sculpting procedures were performed in 2019.9 Approximately 26% (257,868) were cryolipolysis, representing a more than 3-fold increase since 2012.9,10 The popularity of NIBC stems from its ability to deliver fat reduction noninvasively without the need for anesthesia and a faster recovery time compared with invasive liposuction.11,12
Cryolipolysis is the process by which controlled cooling extracts heat from subcutaneous tissue to induce selective adipocyte cell death, thereby reducing the thickness of the subcutaneous fat layer.13-16 There is also clinical evidence of skin tightening and texture improvement in cryolipolysis-treated areas, along with immunohistochemical evidence that neocollagenesis may play a role.16-19 It is thus also reasonable to assume that further enhancement of the skin appearance can be achieved by applying topical treatments that target multiple relevant processes following cryolipolysis.1,20
To characterize the effect of FTB as an adjunct to NIBC procedures, we conducted a pilot, open-label, single-site study of subjects who had pre-elected to undergo cryolipolysis on the inner thighs, back/bra fat, and/or submental areas. The objective of the study was to evaluate the safety and efficacy of FTB as an adjunct to NIBC, especially concerning post-procedure improvements in body skin firmness and texture.
MATERIALS AND METHODS
Study Design
This was an open-label, single-site, single-arm, 12-week pilot study to evaluate the safety and efficacy of FTB when applied twice daily for 12 weeks following cryolipolysis. Scheduled study visits occurred on days -28 to 1 (screening / enrollment), day 1 (baseline), day 14 (week 2), day 42 (week 6), and day 84 (week 12). Screening and enrollment could be part of the baseline visit. The study was conducted in accordance with guidelines for the protection of human subjects as outlined in 21 CFR 50, the accepted standards for Good Clinical Practice. The study protocol and all relevant addenda were reviewed and approved by Aspire IRB, Santee, CA. All subjects provided written informed consent prior to enrollment and study participation.
Study Population
Subjects 20 to 65 years of age, with Fitzpatrick skin types I-VI, who had pre-elected to receive cryolipolysis bilaterally on the inner thighs, back/bra fat, and/or submental regions were eligible to participate in the study. Inclusion requirements included general good health, absence of a disease state/condition that might impair study assessments or increase subject risk, and a willingness to maintain body weight within 5% of baseline weight. Potential subjects were excluded if they were pregnant, nursing, or planning to become pregnant; had any conditions that would make study participation unsafe or impair study assessments; had any contraindication to the body contouring device usage; had undergone invasive or noninvasive fat reduction procedures in the treatment area within the previous 6 months; or had excessive skin laxity in the treatment area(s).
Study Treatment
After study admission, subjects underwent their pre-elected cryolipolysis treatments on day 1 (baseline) after completing baseline pretreatment assessments. All subjects pre-elected, and were candidates for, CoolSculpting or CoolSculpting Elite (Zeltiq Aesthetics, Inc., an AbbVie Company, Pleasanton, CA). Subjects were offered the option to undergo an additional cryolipolysis treatment at week 2 or week 6. The investigator applied FTB to the cryolipolysis-treated area(s) during the same treatment visit using a prespecified number of US quarter dollar-sized amounts (quantity of product). Subjects subsequently applied FTB twice daily (morning and evening) commencing the day after the cryolipolysis treatment visit by smoothing the product onto the cryolipolysis-treated area until fully absorbed for 12 weeks. Adherence to the prescribed treatment was confirmed by assessing the amount used (by weight) at each study visit.
Assessments
Body skin texture and body skin firmness were graded separately by investigators on 10-point scales and assigned to categories: none (score of 0), mild (1-3), moderate (4-6), or severe (7-9). For body skin texture, scoring ranged from none (score of 0; no roughness or crepey texture of the treatment area; skin is completely smooth) to severe (7-9; marked roughness and/or crepey texture of the treatment area). For body skin firmness, scoring ranged from none (0; no sagging or droopy appearance of the treatment area; area appears completely smooth, firm, and taut) to severe (7-9; marked sagging and/or droopy, loose skin appearance of the treatment area). Whenever possible, each subject was graded by the same investigator throughout the study.
Each subject completed a self-assessment questionnaire comprising a series of statements about effectiveness immediately after FTB use (8 statements), effectiveness with continued FTB use throughout the study (15 statements), and product attributes (10 statements). Subjects evaluated each statement on a 4-level scale ("agree strongly" to "disagree strongly"). The questionnaire also included a single statement regarding overall satisfaction with treatment, ranging from "excellent" (very satisfied) to "poor" (not satisfied at all).
Two-dimensional (2D) imaging employed the Canfield IntelliStudio and accompanying instructions (Canfield Site User Manual; Canfield Scientific, Parsippany, NJ) to capture and compare digital images of the treated areas before and after cryolipolysis and FTB treatment.
Investigator assessments and 2D imaging were conducted at baseline (day 1; prior to body contouring procedure[s]) and on days 14, 42, and 84. Self-assessment questionnaires were administered on days 14, 42, and 84. All assessments were completed within +/- 3 days of the target day.
The occurrence of FTB-related adverse events (AEs) and serious AEs (SAEs) was based on spontaneous subject reports (subjects were asked to report any adverse reactions or symptoms) or reports during study visits. Each AE/SAE report was reviewed by the investigator to assess AE severity, relationship to the study treatment (ie, unlikely/possible/probable), and resolution.
Statistical Methods
Because this was a pilot study, no formal sample size calculations were performed. All efficacy and safety analyses were conducted on the intent-to-treat (ITT) population, defined as subjects who completed the baseline visit and at
