Effects of Stabilized Retinaldehyde on Aging Skin: A Split-Face Study

Multimodal Assessment of Structural and Spectral Changes in Aging Skin Induced by Topical Application of Stabilized Retinaldehyde at 0.1% and 0.05%: A 24-Week Split-Face Study

The goal of this clinical trial is to learn if retinaldehyde cream improves the appearance of aging skin in women aged 30 to 60 years. Retinaldehyde is a form of vitamin A that the skin can convert into retinoic acid, which is known to help with skin aging. The study tested two strengths of retinaldehyde cream: a stronger version with 0.1% retinaldehyde and a weaker version with 0.05% retinaldehyde.

The main questions the study aimed to answer were: whether retinaldehyde cream improves skin hydration and reduces oiliness, whether it improves skin firmness and elasticity, whether it reduces wrinkles and improves skin texture, whether it reduces uneven skin tone and pigmentation, and whether the stronger 0.1% cream works better than the weaker 0.05% cream.

Researchers compared the two cream strengths by applying them to opposite sides of the same face. The stronger 0.1% cream was applied to the left side and the weaker 0.05% cream was applied to the right side. This approach allowed researchers to compare the two strengths directly in the same person under the same conditions.

56 women with visible signs of aging skin took part in the study at the Medical University of Silesia in Poland. One participant left the study early due to skin irritation. The remaining 55 women completed all 24 weeks of the study.

Participants apply the creams in the evening, starting with twice a week for the first 2 weeks, then increasing to 3 times a week in week 3 and 4 times a week in week 4, based on skin tolerance, for 24 weeks total. They also used a provided skincare routine every day, which included a lipid face cream, a cleansing lotion, and a sunscreen with SPF 50 to protect their skin during the study.

Participants were assessed 3 times: before starting the creams, after 12 weeks of use, and after 24 weeks of use. At each visit, researchers measured skin hydration, oiliness, elasticity, firmness, wrinkle depth, skin density, skin color, and other skin properties using a range of specialized skin measurement tools. Neither the participants nor the researchers assessing outcomes knew which cream strength was applied to which side of the face.

Study Overview

• Status: Completed
• Conditions: Skin Aging; Photoaging
• Intervention / Treatment: Other: Stabilized retinaldehyde 0.1%; Other: Stabilized retinaldehyde 0.05%

Detailed Description

This study investigated the effects of topically applied stabilized retinaldehyde (RAL) at two concentrations (0.1% and 0.05%) on aging skin in 56 women (55 completing the study) aged 30-60 years (mean age 44.25 ± 8.1 years) with visible signs of photoaging including fine lines, wrinkles, pigmentation disorders, seborrhea, and loss of skin firmness.

A 24-week, double-blind, split-face design was employed. The 0.1% RAL formulation was applied to the left side of the face and the 0.05% formulation to the right side. Application frequency started with twice weekly for the first 2 weeks, increasing to three times per week in week 3 and four times per week in week 4, based on skin tolerance. Both formulations contained stabilized retinaldehyde encapsulated in a cyclodextrin-glycosaminoglycan complex to enhance stability and provide controlled transdermal delivery. The tested products were commercially available formulations provided by the study collaborator. All participants followed a standardized background skincare regimen consisting of a lipid cream, cleansing lotion, and SPF 50 sunscreen throughout the study period.

Skin assessments were performed at baseline (T0), after 12 weeks (T1), and after 24 weeks (T2) using a multimodal diagnostic approach at the Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia.

Biophysical measurements included stratum corneum hydration (Corneometer CM 825), sebum excretion rate (Sebumeter SM 815), and melanin and erythema indices (Mexameter MX 18). Structural assessments were performed using high-frequency ultrasound (DUB SkinScanner, 50 MHz) to evaluate skin density and epidermal thickness, and the Cutometer MPA 580 to assess skin viscoelasticity and elasticity parameters (R2, R5, R7, Q1, Q2). Wrinkle depth and surface parameters were evaluated using Antera 3D imaging. Optical and imaging assessments included colorimetric analysis of L*, a*, and b* values (Antera 3D), hyperspectral imaging across 400-1000 nm spectral range (SPECIM IQ), and Gray Level Co-Occurrence Matrix (GLCM) texture analysis including contrast and homogeneity of standardized clinical photographs (Fotomedicus system).

The study aimed to determine whether stabilized RAL induces measurable structural, vascular, spectral, and optical changes in aging skin, and to compare the dose-dependent efficacy of 0.1% versus 0.05% concentrations across all measured parameters.

One participant withdrew from the study due to facial erythema and discomfort. No other serious adverse events were reported.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Sosnowiec, Poland, 41-205
    • Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Sosnowiec, Poland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 30-60 years
• Presence of wrinkles, dark spots, acne, seborrhea
• Decreased skin firmness

Exclusion Criteria:

• Exacerbated active atopic dermatitis on the face
• Pregnancy
• Skin infections
• Numerous erosions or excoriations on facial skin
• No aesthetic medical treatments within the preceding 6 months
• Administration of botulinum toxin within the preceding 3 months
• Irritated, dry skin
• Irritated or excessively dry skin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retinaldehyde 0.1% (Left Side); Stabilized retinaldehyde 0.1% formulation applied to the left side of the face for 24 weeks. Application frequency started with twice weekly for the first 2 weeks, increasing to three times per week in week 3 and four times per week in week 4, based on skin tolerance.	Other: Stabilized retinaldehyde 0.1%; Stabilized retinaldehyde 0.1% encapsulated in a cyclodextrin-glycosaminoglycan complex, formulated as a topical cosmetic cream, applied to the left side of the face. Application frequency started with twice weekly for the first 2 weeks, increasing to three times per week in week 3 and four times per week in week 4, based on skin tolerance, for a total of 24 weeks.; Other Names: Retinal 0.1%
Experimental: Retinaldehyde 0.05% (Right Side); Stabilized retinaldehyde 0.05% formulation applied to the right side of the face for 24 weeks. Application frequency started with twice weekly for the first 2 weeks, increasing to three times per week in week 3 and four times per week in week 4, based on skin tolerance.	Other: Stabilized retinaldehyde 0.05%; Stabilized retinaldehyde 0.05% encapsulated in a cyclodextrin-glycosaminoglycan complex, formulated as a topical cosmetic cream, applied to the right side of the face. Application frequency started with twice weekly for the first 2 weeks, increasing to three times per week in week 3 and four times per week in week 4, based on skin tolerance, for a total of 24 weeks.; Other Names: Retinal 0.05%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Hydration	Stratum corneum hydration measured using Corneometer CM 825 (Courage+Khazaka, Germany). Three consecutive measurements taken at predefined anatomical landmarks on both sides of the face.	Baseline and 24 weeks
Sebum Excretion Rate	Sebum levels measured using Sebumeter SM 815 (Courage+Khazaka, Germany). Single measurement at each predefined anatomical site applied with constant pressure of 10 N for 30 seconds.	Baseline and 24 weeks
Melanin Index	Melanin content measured using Mexameter MX 18 (Courage+Khazaka, Germany). Three consecutive measurements taken at predefined anatomical landmarks.	Baseline and 24 weeks
Erythema Index	Erythema measured using Mexameter MX 18 (Courage+Khazaka, Germany). Three consecutive measurements taken at predefined anatomical landmarks.	Baseline and 24 weeks
Skin Density and Epidermal Thickness	Assessed using high-frequency ultrasound DUB SkinScanner 50 MHz. Skin density measured using ROI function directly beneath epidermis. Epidermal thickness calculated in millimeters based on A-scan.	Baseline and 24 weeks
Skin Viscoelasticity and Elasticity	Assessed using Cutometer MPA 580 (Courage+Khazaka, Germany) with 2 mm probe. Parameters R2, R5, R7, Q1, Q2 extracted from deformation curves.	Baseline and 24 weeks
Wrinkle Depth and Surface Parameters	Assessed using Antera 3D imaging system (Miravex Limited, Ireland) with multi-directional illumination. ROIs of 20x20 mm at predefined anatomical landmarks.	Baseline and 24 weeks
Colorimetric Parameters	L*, a*, b* values measured using Antera 3D imaging system (Miravex Limited, Ireland). Data extracted from standardized ROIs of 20x20 mm.	Baseline and 24 weeks
Skin Texture - GLCM Analysis	Contrast and homogeneity assessed using Gray Level Co-Occurrence Matrix (GLCM) analysis of standardized clinical photographs taken with Fotomedicus system (Elfo, Poland). ROIs of 200x200 pixels extracted from central cheek coordinates.	Baseline and 24 weeks
Hyperspectral Imaging	Reflectance and hemoglobin variability assessed using SPECIM IQ hyperspectral camera (Specim, Finland), spectral range 400-1000 nm, spectral resolution 5 nm. ROIs of 100x100 pixels from predefined cheek coordinates.	Baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Medical University of Silesia
• Collaborators: PH DOCTOR N&D Wiśniewscy S.K.A.
• Investigators: Principal Investigator: Sławomir Wilczyński, Prof. PhD, Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Sosnowiec, Poland

Publications and helpful links

General Publications

• Deda A, Odrzywolek W, Lebiedowska A, Banys A, Bozek M, Kuca D, Wisniewska N, Wcislo-Dziadecka D, Wilczynski S. Comparative Evaluation of Topical Stabilized Retinaldehyde 0.1% vs. 0.05% on Skin Biophysical and Biomechanical Parameters. Skin Res Technol. 2026 Feb;32(2):e70326. doi: 10.1111/srt.70326.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Retinoid; Hyperspectral imaging; Skin hydration; Split-face study; Retinaldehyde; GLCM texture analysis
• Other Study ID Numbers: PCN/0022/KB1/11/I/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in publications will be shared upon reasonable request. This includes data necessary to reproduce the findings presented in the articles. Data will be available after publication, subject to institutional policies, ethical approval, and applicable data protection regulations. No directly identifiable data will be shared. Supporting documents such as the study protocol and statistical analysis plan may also be made available upon request.
• IPD Sharing Time Frame: Data will be available beginning 3 months after publication of the final study results and will remain available for 5 years.
• IPD Sharing Access Criteria: Access to de-identified individual participant data will be provided to qualified researchers upon reasonable request. Requests should include a brief description of the research purpose. Requests will be reviewed by the study investigators. Data will be shared in accordance with institutional policies, ethical considerations, and applicable data protection regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No