5fluorouracil for Advanced Photoaging

Phase 3

• Conditions: Photoaging; Actinic Keratosis
• Interventions: Procedure: 5-fluoruracil

• Registration Number: NCT01405144
• Lead Sponsor: Federal University of São Paulo

Brief Summary

It is well known the efficacy of 5% 5-fluoruracil for multiple and superficial actinic keratosis (AKs)treatment. Recently its additional benefit for advanced and severe photoaging while treating Aks was reported.

The aim of this study is to compare the efficacy and safety of the two modalities of 5% 5-FU use for forearms photoaging.

Detailed Description

The use of 5% 5-fluorouracil (5-FU) cream, twice a day, during 3 weeks represents a classic treatment for multiple and superficial AKs. The main adverse event is the severe skin irritation leading to interruption of the treatment in some cases. In the last decade a superficial pulse-peeling using it as agent in sequential applications was described. This modality of treatment has been demonstrated efficacy and better tolerability.

The improvement of the overall aspect of photodamaged skin is observed while treating multiple AKs.

There are no comparative study between the two types of 5% 5-FU use. So that is the purpose of our clinical trial.

Study Timeline

• Study Start: 2010-08
• Status Verified: 2011-05
• Study First Submitted: 2011-07-05
• Study First Submitted QC: 2011-07-28
• Last Update Submitted: 2011-07-28
• Study First Posted: 2011-07-29
• Last Update Posted: 2011-07-29
• Primary Completion: 2011-09
• Study Completion: 2012-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Healthy Men and women, aged from 50 to 75 anos;
2. Phototype I a III (Fitzpatrick Classification);
3. Advanced photoaging on forearms, with multiple superficial actinic keratosis;
4. Agreement with no sun exposure during the study and
5. Agreement with study conditions,capacity to understand and follow the orientations and form consent signature.

Exclusion Criteria

1. Topical treatment with:

   • tretinoin in the last 6 months ;
   • other retinoids, alpha-hydroxyacids, poli-hydroxyacids, beta-hydroxyacids and ascorbic acid in the last 3 months;

2. Treatment by chemical peeling, microdermabrasion and non-ablative laser in the last 3 months;

3. Treatment with systemic retinoid in the last 6 months ;

4. Chemotherapy in the last 3 months;

5. Hypersensibility to parabens;

6. Infectious or inflammatory dermatosis on forearms;

7. Clinical evidence of immunosuppression and

8. Presence of photodermatosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
5% 5-fluoruracil cream	5-fluoruracil	30 patients will use 5% 5-fluoruracil cream, twice a day, during 3 weeks, in one randomized forearm
5% 5-fluoruracil peeling	5-fluoruracil	The same 30 patients will be submitted to 4 applications of 5% 5-fluoruracil superficial peeling in the other forearm

Primary Outcome Measures

Name	Time	Method
Change in Photographic Evaluation	0, 60, 180 days	Photographic blinded evaluation by two independent observers, comparing modifications of forearms skin overall aspect before and after 60 and 180 days of the treatments. The following 5 point scale will be used: -2=much worse; -1=worse; 0=inlatered; 1=better, 2= much better
Change in Microscopic Evaluation	0, 180 days	Skin biopsies will be performed and coloration by hematoxilin-eosin, Verhoeff, Tricromio Masson , Picrosirius and biomarkers (p53, bcl2, collagen 1)will be used. The modifications on corneal layer and epidermal thickness, dermal elastotic material and collagen deposition and biomarkers expression will be evaluated by digital quantitative analysis, comparing the findings before (day 0) and after (day 180)treatments.

Secondary Outcome Measures

Name	Time	Method
Inflammatory Skin Reaction	30 day	Comparison between treatments on inflammatory skin reaction will be performed by expression of interleucin-1, using immunohistochemistry
Occurence and Evaluation of Adverse Events	30, 60, 180 days	Predictable and unpredictable side effects and their intensity related by patient and/or observed by investigator will be analized and compared between the treatments
Change in Patient Opinion	0, 30, 60, 180 days	Patient opinion concerning modification on forearms skin overall aspect, using a 5 point scale: -2=much worse; -1=worse; 0=inaltered; 1=better, 2= much better, comparing day 0 to 60, 60 to 180 and 0 to 180.
Change in Investigator Clinical Evaluation	0, 30, 60, 180 days	Investigator efficacy evaluation through actinic keratosis counting, on days 0, 30, 60 and 180 as weel as modification on forearms skin overall aspect. That will be performed by comparision of skin examination on days 60 and 180 to photography captured on days 0 and 60, i.e, 0 to 60, 60 to 180 and 0 to 180, using a 5 point scale: -2=much worse; -1=worse; 0=inaltered; 1=better, 2= much better
Change in Forearm Photoaging Classification	0, 60, 180 days	A classification will be created and validated by investigators and five independent observers previously to classify forearm photoaging. After validation it will be applied to study subjects on days 0, 60 and 180 to evaluate modification on the forearm photoaging grade for each tretament.

Trial Locations

Locations (1)

Edileia Bagatin; 🇧🇷 Sao Paulo, SP, Brazil