Study of oral retinol, with or without medical sun protection, in patients with actinic keratosis

ISRCTN	ISRCTN42565762
DOI	https://doi.org/10.1186/ISRCTN42565762
Sponsor	Cantabria Labs Difacooper
Funder	Cantabria Labs Difacooper

Submission date: 13/05/2026
Registration date: 18/05/2026
Last edited: 18/05/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Skin and Connective Tissue Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Massimo Milani
Public, Scientific, Principal investigator

Via Milano, 160
Caronno Pertusella
21042
Italy

Phone	+39 (0)280030205
Email	massimo.milani@difacooper.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Prevention
Scientific title	Efficacy and safety of oral retinol, alone or combined with medical photoprotection, in patients with actinic keratosis: a randomized, controlled, prospective, multicentric study
Study objectives	The aim of this study was to evaluate the efficacy and tolerability of oral vitamin A, administered alone (the "In" strategy) or in combination with medical photoprotection (a film-forming medical device containing SPF 50+ sunscreen and piroxicam 0.8%, the “In & Out" strategy), in modulating the progression of actinic damage in subjects with mild-to-moderate actinic keratosis, compared with a control group.
Ethics approval(s)	Approved 12/01/2023, Medizioni (Via Monte delle Gioie, Roma, 00199, Italy; +39 (0)631050390; medizioni@medizioni.it), ref: DC 01-2023
Health condition(s) or problem(s) studied	Actinic keratosis (AK)
Intervention	Participants were randomized into three groups using a computer-generated allocation sequence. The patients were allocated across three treatment groups in a 1:1:1 ratio. Group A received oral vitamin A (50,000 IU daily for 6 consecutive months), in addition to standardized sun-protection recommendations. These included limiting sun exposure, avoiding direct sunlight between 10:00 and 14:00, wearing protective clothing and wide-brimmed hats, avoiding tanning devices, and applying sunscreen with SPF ≥30 daily. Group B received oral vitamin A at the same dosage in combination with medical photoprotection, consisting of a film-forming medical device containing SPF 50+ sunscreen and piroxicam 0.8%, applied twice daily to the face and scalp for 6 months. Group C (control group) received only standardized sun-protection recommendations.
Intervention type	Mixed
Primary outcome measure(s)	Treatment efficacy measured using the Actinic Keratosis and Severity Index at baseline, month 3 (T3), month 6 (T6, end of the treatment), month 9 (T9, follow-up)
Key secondary outcome measure(s)	Global clinical efficacy measured using using a five-point scale ranging from “very good” to “very poor,” based on overall changes in AK lesions, at baseline, month 3 (T3), month 6 (T6, end of the treatment), month 9 (T9, follow-up) Global lesion clearance measured using a similar five-point scale, specifically focused on lesion resolution at baseline, month 3 (T3), month 6 (T6, end of the treatment), month 9 (T9, follow-up) Treatment tolerability measured using a four-point scale, where 0 indicated excellent tolerability (no symptoms) and 3 indicated poor tolerability (severe pain, itching, or burning), at baseline, month 3 (T3), month 6 (T6, end of the treatment), month 9 (T9, follow-up) Safety measured using systematic documentation of all adverse events at baseline, month 3 (T3), month 6 (T6, end of the treatment), month 9 (T9, follow-up) In a predefined subgroup of 13 patients from Groups A and B: non-invasive imaging analysis including epidermal and dermal thickness, stratum corneum thickness, and evaluation of keratinocyte atypia, graded as mild, moderate, or severe, measured using line-field confocal optical coherence tomography (LC-OCT) at month 3
Completion date	15/04/2026

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	105
Total final enrolment	117
Key inclusion criteria	Adults aged 18 to 80 years with up to six clinically diagnosed AK lesions
Key exclusion criteria	1. Presence of more than six AK lesions 2. Use of nicotinamide within 6 months prior to enrollment 3. History of skin cancer 4. Organ transplantation 5. Pregnancy or lactation
Date of first enrolment	01/04/2023
Date of final enrolment	13/05/2025

Locations

Countries of recruitment

Italy

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Editorial Notes

14/05/2026: Study's existence confirmed by Medizioni.