Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis

NCT02278861 | Completed Phase 2 DMC

• 1 other identifier: UFG 133/11
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Actinic keratosis (AKs) are premalignant disorders that can evolve into skin cancer. To prevent their development, a study is being conducted with oral isotretinoin and topical tretinoin to verify what drug is the most effective and has the best security profile for these patients. Along with these treatments, cryotherapy with liquid nitrogen and sunscreens will be part of the treatment. The study will have the duration of 10 months. In the first four months, the AKs will be counted and treated with cryotherapy (face and arms) and sunscreens FPS 60 will be used. After it, the patients will return (the AKs will be counted), a new session of cryotherapy will be performed and they will be randomized into two groups: one group using oral isotretinoin 10mg/day ( ISO: 30 patients) and the other one using tretinoin 0,05% cream (AR: 30 patients) applied on face and arms. Skin biopsies will be done for all 60 patients at the beginning of the treatment with retinoids (isotretinoin and tretinoin). After six months of treatment with retinoids, the study will be stopped, AKs will be counted again and skin biopsies will be done. Patients in the group ISO (oral isotretinoin) also have to make blood tests at the beginning, two months and after six months of the treatment. Clinical (AK counting), histological (improvement of parts of the skin) and immunohistochemical parameters will be evaluated to see what drug is more effective for prevention of AKs.

Conditions

Actinic Keratosis

Keywords

actinic keratosis; tretinoin; isotretinoin; cryotherapy; sun protection factor; clinical clearance

Outcome Measures

Primary Outcomes (1)

• Reduction in the counting of actinic keratosis in the face and forearms

  The actinic keratosis (AKs) will be counted by the same evaluator twice, in different moments at the same day, at the beginning of the study, after 4 months and at the end (10 months)

  at the beginning (T0), 120 days (T120) and 300 days (T300)

Secondary Outcomes (5)

• Reduction in the thickness of the stratum corneum

  4 months (T120) and 10 months (T300) of the study

• Increase in the epithelium thickness

  4 months (T120) and 10 months (T300) of the study

• Reduction in the expression of p53 protein

  4 months (T120) and 10 months (T300) of the study

• Reduction in the expression of the Bcl-2 protein

  4 months (T120) and 10 months (T300) of the study

• Increase in the expression of Bax protein

  4 months (T120) and 10 months (T300) of the study

Other Outcomes (3)

• Reduction in the Dermatology Life Quality Index (DLQI)

  at the beginning, with 4 months (T120) and 10 months (T300) of the study

• Clinical adverse events of tretinoin

  4 months (T120) and 10 months (T300) of the study

• Laboratory alterations in patients treated with low dose oral isotretinoin (10mg/day)

  4 months (T120), 6 months (T180) and 10 months (T300). If there were alterations, the laboratory tests were done monthly

Study Arms (2)

Oral isotretinoin 10mg/day

ACTIVE COMPARATOR

Oral isotretinoin 10mg/day for 6 months The dose could be reduced if there were any significant laboratory alterations or clinical adverse events, along with sunscreen FPS 60 every 3 hours during the day.

Drug: Oral isotretinoin; Drug: Sunscreen FPS 60

Tretinoin 0,05% cream

ACTIVE COMPARATOR

An every other night application of tretinoin 0,05% cream in the face and forearms for 6 months, along with sunscreen FPS 60 every 3 hours during the day. If there were any clinical adverse events the drug could be reduced to twice a week.

Drug: Tretinoin 0,05% cream; Drug: Sunscreen FPS 60

Interventions

Oral isotretinoin DRUG

Oral isotretinoin - 10mg/day (one pill) after lunch for six months

Also known as: Acnova

Oral isotretinoin 10mg/day

Tretinoin 0,05% cream DRUG

Topical tretinoin 0,05% cream - applied every other night in the face and forearms for six months

Also known as: Vitacid 0,05% cream

Tretinoin 0,05% cream

Sunscreen FPS 60 DRUG

Sunscreen FPS 60 applied on sun exposed areas every 3 hours daily

Also known as: Skin Block 60 Fluide Extreme

Oral isotretinoin 10mg/day; Tretinoin 0,05% cream

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signature of the Free and Clarified Consent Term before any procedure of the study;
• Men and women, aged 50-75 years, in good health;
• Women in menopause for 1 year or more;
• Phototypes I-IV by Fitzpatrick classification;
• Glogau photodamage classification scale from moderate to severe
• At least 10 and maximum 60 visible and/or palpable actinic keratosis, in the face and forearms, in a standardized distribution;
• Absence of topical treatment in the face and forearms, except sunscreens, with:
• tretinoin in the last 6 months;
• alphahydroxyacids, polyhydroxyacids, betahydroxyacids and ascorbic acid in the last 3 months;
• drugs or procedures that may change the natural evolution of actinic keratosis, such as imiquimod 5% cream, diclofenac 3% in hyauronic acid gel, photodynamic therapy, 5-FU, in the last 6 months;
• Absence of previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;
• Absence of previous treatment with oral retinoids in the last 6 months;
• Absence of anti-cancer chemotherapy in the last 3 months;
• Absence of hypersensitivity to parabens (present in the majority of drugs as a preserving agent);
• Absence of infectious or inflammatory diseases in the face and forearms;

You may not qualify if:

• For all patients:
• Men and women who dón't agree with the terms of the research or without ability to understand and/or follow strictly the conditions of the study, without availability to understand and attend the periodical evaluations or who decline to sign the Free and Clarified Consent Term;
• Patients with less than 10 and more than 60 actinic keratosis in the face and forearms;
• Fertile, pregnant or lactating women;
• Fitzpatrick phototypes V e VI ;
• Topical treatment in the face and forearms, except sunscreens, with:
• tretinoin in the last 6 months;
• alphahydroxyacids, polyhydroxyacids, betahydroxyacids and ascorbic acid in the last 3 months;
• drugs or procedures that may change the natural evolution of actinic keratosis, such as imiquimod 5% cream, diclofenac 3% in hyauronic acid gel, photodynamic therapy, 5-FU, in the last 6 months;
• Previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;
• \. Previous treatment with oral retinoids in the last 6 months
• For the isotretinoin group (ISO):
• Presence of significative hepatic laboratory alterations (elevated liver enzymes twice ashigh as the upper normal limit;
• Diabetic patients, with fast glucose values superior to 110mg/dl;
• Significant lipid profile alterations (triglycerides \> 300 mg/dl; total cholesterol\> 250 mg/dl);

Sponsors & Collaborators

• Universidade Federal de Goias: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Theraskin: collaborator
• Germed Pharma: collaborator

Study Sites (1)

Dermatology Outpatient Clinic - Hospital das Clínicas - Federal University of Goias (UFG)

Goiânia, Goiás, 74605-020, Brazil

Location

Related Publications (2)

• Ianhez M, Fleury LF Jr, Miot HA, Bagatin E. Retinoids for prevention and treatment of actinic keratosis. An Bras Dermatol. 2013 Jul-Aug;88(4):585-93. doi: 10.1590/abd1806-4841.20131803.

  PMID: 24068130 RESULT

• Weinstock MA, Bingham SF, Cole GW, Eilers D, Naylor MF, Kalivas J, Taylor JR, Gladstone HB, Piacquadio DJ, DiGiovanna JJ. Reliability of counting actinic keratoses before and after brief consensus discussion: the VA topical tretinoin chemoprevention (VATTC) trial. Arch Dermatol. 2001 Aug;137(8):1055-8.

  PMID: 11493098 RESULT

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Isotretinoin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Edileia Bagatin, MD, PhD

  Federal University of São Paulo UNIFESP

  STUDY CHAIR

• Hélio A Miot, MD, PhD

  University of Paulista State - Julio de Mesquita Filho, UNESP

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, MD, MsC

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: October 30, 2014
• Study Start: November 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 30, 2014

Record last verified: 2014-10

Locations

BR (1)