Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Universidade Federal de Goias
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Germed Pharma; Theraskin
• Treatments: Isotretinoin; Sunscreening Agents; Tretinoin

Criteria

Inclusion Criteria:

1. Signature of the Free and Clarified Consent Term before any procedure of the study;

2. Men and women, aged 50-75 years, in good health;

3. Women in menopause for 1 year or more;

4. Phototypes I-IV by Fitzpatrick classification;

5. Glogau photodamage classification scale from moderate to severe

6. At least 10 and maximum 60 visible and/or palpable actinic keratosis, in the face and forearms, in a standardized distribution;

7. 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;

8. Absence of previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;

9. Absence of previous treatment with oral retinoids in the last 6 months;

10. Absence of anti-cancer chemotherapy in the last 3 months;

11. Absence of hypersensitivity to parabens (present in the majority of drugs as a preserving agent);

12. Absence of infectious or inflammatory diseases in the face and forearms;

13. Absence of immunossupression;

14. Absence of photodermatosis;

15. Agreement in avoiding sun exposure during the research;

16. Agreement in not performing any other kind of treatment that could change the natural history of actinic keratosis; and

17. Agreement with the study conditions, ability to understand and follow strictly the given orientations, availability to attend the periodical evaluations.

For the isotretinoin group (ISO):

1. Absence of history of isotretinoin hypersensitivity;

2. Avoid alcohol intake and;

3. Absence of previous and actual history of rheumatologic diseases.

For the tretinoin group (AR):

1. Absence of history of tretinoin hypersensitivity;

Exclusion Criteria:

For all patients:

1. 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;

2. Patients with less than 10 and more than 60 actinic keratosis in the face and forearms;

3. Fertile, pregnant or lactating women;

4. Fitzpatrick phototypes V e VI ;

5. 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;

6. Previous treatment in the face and forearms with chemical peels and microdermabrasion, in the last 6 months;

8. Previous treatment with oral retinoids in the last 6 months

For the isotretinoin group (ISO):

1. Presence of significative hepatic laboratory alterations (elevated liver enzymes twice ashigh as the upper normal limit;

2. Diabetic patients, with fast glucose values superior to 110mg/dl;

3. Significant lipid profile alterations (triglycerides > 300 mg/dl; total cholesterol> 250 mg/dl);

4. Low count of white blood cells (leukocytes < 3000/mm3);

5. History of hypersensitivity to isotretinoin and parabens;

6. Alcohol intake;

7. Previous or actual history of rheumatologic diseases;

8. Anticancer chemotherapy in the last 3 months;

9. Previous history of hypervitaminosis A;

10. Previous history of bone or muscular diseases;

11. Patients who are in use or may use the following drugs (risk of drug interaction):

• tetracyclines and derivatives - in the last 7 days;

• vitamin A - in the last 30 days;

• carbamazepine - in the last 7 days.