Safety and effectiveness of 0.1% tretinoin as aging related conditions.

Not yet recruiting

• Conditions: Atrophic disorder of skin, unspecified,

• Registration Number: CTRI/2025/06/088719
• Lead Sponsor: H&H Pharmaceutica LLP

Brief Summary

Skinaging is a complex and multifactorial biological process that leads to gradualdeterioration in the skin’s structure, function and appearance. Common clinicalmanifestations include fine lines, wrinkles, dyspigmentation, laxity, and lossof elasticity. This process is influenced by intrinsic (endogenous) factorssuch as genetics, cellular senescence, and hormonal changes, as well asextrinsic (exogenous) factors including ultraviolet (UV) radiation,environmental pollutants, and mechanical stress. These factors contribute tounderlying physiological changes like glycation, oxidative stress,inflammation, impaired DNA repair, and extracellular matrix degradation (Shinet al., 2023; Knaggs et al., 2023).

Topicalantiaging treatments have gained significant popularity in clinicaldermatology, with retinoids—particularly tretinoin—recognized as the goldstandard due to their proven efficacy in reducing fine lines, evening skintone, promoting collagen synthesis, and increasing epidermal turnover (Milosheska & Roskar, 2022; Sitohang etal., 2022).

Tretinoin, a derivative of vitamin A,penetrates the epidermis and binds to intracellular retinoic acid receptors(RARs). These receptors form heterodimers with retinoid X receptors (RXRs),which then bind to retinoic acid response elements (RAREs) in the DNA ofkeratinocytes and fibroblasts. This molecular interaction regulates thetranscription of various genes responsible for skin remodelling and repair.

Through this RAR–RXR–RARE signalling axis,tretinoin upregulates the expression of genes involved in collagen production,including procollagen I and III, thereby enhancing skin firmness and reducingwrinkles. It also boosts skin regeneration by promoting cellular turnover andsupports angiogenesis, which improves oxygen and nutrient delivery to the skin.Simultaneously, tretinoin downregulates processes contributing to photoaging,such as excessive keratinocyte proliferation, matrix metalloproteinases (MMPs)that degrade collagen, pro-inflammatory cytokines like IL-6 and TNF-alpha, andtyrosinase activity, which is involved in melanin synthesis and pigmentation.

The primary target cells of tretinoin arekeratinocytes in the epidermis and fibroblasts in the dermis. Keratinocytesinfluence epidermal thickness and renewal, while fibroblasts are central toextracellular matrix (ECM) maintenance, producing collagen and elastin. Bymodulating gene expression in both cell types, tretinoin not only stimulatescollagen synthesis and inhibits its degradation but also reduces inflammationand pigmentation, making it a fundamental agent in dermatologic anti-agingtreatment strategies (Uchida et al., 2003; Mambwe et al., 2025).

Detailed Description

Not available

Study Timeline

• Study Start: 2025-06-26
• Last Update Posted: 2025-11-06

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 1.Male or female subjects aged 35 to 70 years with visible signs of skin aging.
• 2.Subjects having one or more signs of aging such as wrinkles, fine lines, uneven skin tone, or mild pigmentation.
• 3.Subjects belonging to Fitzpatrick skin types III to V.
• 4.Subjects willing and able to comply with the study protocol and abstain from any anti-aging treatments or topical medications (other than the investigational product) during the 16-week study period.
• 5.Subjects must provide written informed consent prior to participation.
• 6.If using make-up, subjects must have used the same brand/type for at least 14 days prior to study entry and agree not to change the product or usage frequency during the study.

Exclusion Criteria

• 1.Subjects with known hypersensitivity or allergy to tretinoin, retinoids, or any ingredients in the investigational product.
• 2.Women who are pregnant, lactating, or planning pregnancy during the study period.
• 3.Subjects with history of cosmetic or dermatologic procedures within 3 months prior to baseline (e.g., chemical peels, microdermabrasion).
• 4.Subjects intended to use anti-aging products (topical or oral) other than investigation product during the study.
• 6.Subjects having baseline irritation score of 3 (severe) based on investigator’s assessment.
• 7.Subjects with history of use of oral retinoids within 6 months before baseline or planned use during the study.
• 8.Subjects who used hormonal contraceptives within 3 months prior to baseline.
• 9.Subjects undergone prior laser therapy or phototherapy within the past 6 months to study entry.
• 10.Subjects who underwent cosmetic treatments (e.g., facials) within 14 days prior to study start that may influence study outcomes.
• 11.Subjects who are current smokers or history of tobacco use exceeding 10 pack-years.
• 12.Unstable, clinically significant, or life-threatening disease that may pose a risk to the subjects or affect the study results, as judged by the investigator.
• 13.Subjects who are regular engagement in activities involving prolonged sun exposure or exposure to extreme weather conditions (e.g., wind, cold).
• 14.Subjects who are engaged in alcohol consumption or use of recreational/abusive drugs (e.g., cannabinoids, cocaine, barbiturates).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in wrinkle severity score (Modified Griffiths Scale or WSRS)	After 4 months
Improvement in skin texture (visual grading)	After 4 months

Secondary Outcome Measures

Name	Time	Method
Wrinkle severity & photoaging grade were assessed using Antera 3D equipment.	Melanin & erythema levels were measured using Dermatcatch.

Trial Locations

Locations (1)

CUTIS Academy of Cutaneous Sciences; 🇮🇳 Bangalore, KARNATAKA, India

CUTIS Academy of Cutaneous Sciences

🇮🇳Bangalore, KARNATAKA, India

Dr Sheethal B M

Principal investigator

8050626321

sheetaldas09@gmail.com