Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis
Information source: Universidade Federal de Goias
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Actinic Keratosis
Intervention: Oral isotretinoin (Drug); Tretinoin 0,05% cream (Drug); Sunscreen FPS 60 (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Universidade Federal de Goias Official(s) and/or principal investigator(s): Edileia Bagatin, MD, PhD, Study Chair, Affiliation: Federal University of São Paulo (UNIFESP) Hélio A Miot, MD, PhD, Study Chair, Affiliation: University of Paulista State - Julio de Mesquita Filho, UNESP
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.
Clinical Details
Official title: Low Dose Oral Isotretinoin Versus Topical Tretinoin for Prevention of Actinic Keratosis in Immunocompetent Patients: a Randomized, Comparative Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Reduction in the counting of actinic keratosis in the face and forearms
Secondary outcome: Reduction in the thickness of the stratum corneumIncrease in the epithelium thickness Reduction in the expression of p53 protein Reduction in the expression of the Bcl-2 protein Increase in the expression of Bax protein
Detailed description:
This study is a randomized controlled trial with 60 men and women (already in menopause for
at least one year), aged 50-75 years. At the beginning, the number of actinic keratosis
(AKs) of face and forearms will be counted and treated with cryotherapy with liquid nitrogen
(LN).The patients will be randomized in two groups: one receiving oral isotretinoin 10mg/day
every day and other receiving tretinoin 0,05% cream applied in the face and arms every other
night, for six months. Along with these treatments, patients will use sunscreens FPS 60 with
UVA and UVB protection. The inclusion criteria will be the presence of at least 10 and
maximum 40 AKs (visible or palpable). Skin biopsies will be performed twice (before and
after treatment with retinoids) for all patients, in the left forearm at a standardized
site. Histological and immunohistochemical with blinded- evaluator analysis will be done.
The main objective of the study is to evaluate clinical, histological and
immunohistochemical effects of retinoids for AK prevention on face and forearms of
immunocompetent individuals. Efficacy evaluation will be measured by improving clinical (AK
counting before and after treatments), histopathological (Hematoxilin-eosin and Verhoeff
staining) and immunohistochemical parameters (markers for carcinogenesis - p53 protein,
Bcl-2 and Bax). The secondary objective is evaluate the tolerability and safety of the drugs
and their impact in quality of life. The safety analysis will be related to adverse events
of the two drugs and the blood tests will be performed in the ISO group patients.
Indirectly, by decreasing the number of AKs and the expression of cutaneous carcinogenesis
markers, a decrease in the risk of squamous cell carcinoma could be infered . This
principle is used by many drugs called chemoprophylactic drugs, and the retinoids are
considered in this group.
Eligibility
Minimum age: 50 Years.
Maximum age: 75 Years.
Gender(s): Both.
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.
Locations and Contacts
Dermatology Outpatient Clinic - Hospital das Clínicas - Federal University of Goias (UFG), Goiânia, Goiás 74605-020, Brazil
Additional Information
Starting date: November 2011
Last updated: October 29, 2014
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