A Prospective, Double-Blinded, Randomized Head-to-Head Clinical Trial of Topical Adapinoid (Oleyl Adapalenate) Versus Retinol
Authors: Nguyen Nhi , Afzal Nasima , Min Mildred , Ahmad Nabeel , Afzal Laila , Burney Waqas , Chambers Cindy J. , Sivamani Raja K. 
Published: November 2024

Abstract

Background
Retinoids, such as retinol, are widely investigated and utilized in skin care products as a treatment for photoaging but their use is limited by tolerability. Adapinoid (oleyl adapalenate, OA) is a novel third generation retinoid that is a pro-drug of adapalene, but there is little research on its effects on photoaging or its tolerability.

Objectives
The purpose of this study is to compare the effects and tolerability of OA 0.5% to retinol 0.5% cream regarding visible signs of facial photoaging including facial wrinkles, fine lines and pigmentation.

Methods
In this 12-week, double-blind, randomized clinical trial, 48 eligible participants were recruited and enroled from the Greater Sacramento region. The study consisted of a baseline and follow-up visits at weeks 4, 8 and 12. Participants were randomized to receive either topical OA 0.5% or retinol 0.5% for 12 weeks. The primary outcome was changes in the appearance of wrinkle severity at 12 weeks. Secondary outcome measures include changes in erythema, skin pigmentation, skin hydration and transepidermal water loss (TEWL).

Results
OA improved wrinkle severity by 9.45% (p &lt; 0.0001) at week 12, whereas retinol improved wrinkle severity by 4.11% (p &lt; 0.001) compared to baseline. When comparing the two treatment groups at week 12, the OA group improved significantly more than the retinol group (p = 0.001). OA decreased pigment intensity at week 12 by 3.88% (p &lt; 0.0001), whereas retinol decreased pigment intensity by 3.15% (p &lt; 0.03) compared to baseline. OA-based improvement in pigment intensity at week 12 was not significantly different from retinol (p = 0.62). OA reduced facial erythema by 13.39% (p &lt; 0.05) at week 12, whereas the retinol group did not have a significant change. OA use led to a 14.92% decrease in TEWL by week 12 (p = 0.07), whereas the retinol group had no significant change. OA was better tolerated than retinol when assessed at all follow-up visits.

Conclusions
OA 0.5% is superior to retinol 0.5% in improving wrinkle severity and similar in improvement of pigment intensity. OA is better tolerated than retinol. Overall, the use of OA as a precursor to adapalene may be an effective method to improving the tolerability of retinoids while maintaining efficacy.

Trial Registration
This study was registered on www.clinicaltrials.gov (NCT05778760).

Plain Language Summary
Skin photoaging is a common skin concern characterized by wrinkles, fine lines, uneven skin and tone. Due to the visible nature of photoaging, there is considerable interest in cosmeceuticals designed to combat photoaging. Retinoids, such as retinol, have significant evidence supporting their use in facial photoaging but they can cause facial irritation as a side effect. Adapinoid (oleyl adapalenate, OA) is a newly available precursor to adapalene and may have potential for use on the skin with similar efficacy to retinol but with less irritation. This study aimed to find out how topical OA compared to retinol. Participants applied either OA or retinol to their facial skin daily and we found that OA improved visible signs of facial ageing and was better tolerated than retinol.