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Actinic KeratosisPhase 2ARISOAKNCT02278861

Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis

A Phase 2 study testing Oral isotretinoin, Tretinoin 0,05% cream and Sunscreen FPS 60 in people with Actinic Keratosis, run by Universidade Federal de Goias at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 to 75 years
Conditions the study is for
Actinic Keratosis
What is being tested?
Oral isotretinoin, Tretinoin 0,05% cream and Sunscreen FPS 60
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteBrazil
Study dates
Nov 2011to May 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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;
  • Absence of immunossupression;
  • Absence of photodermatosis;
  • Agreement in avoiding sun exposure during the research;
  • Agreement in not performing any other kind of treatment that could change the natural history of actinic keratosis; and
  • 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):
  • Absence of history of isotretinoin hypersensitivity;
  • Avoid alcohol intake and;
  • Absence of previous and actual history of rheumatologic diseases.
  • For the tretinoin group (AR):
  • 1. Absence of history of tretinoin hypersensitivity;

Who cannot join

  • 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:
Show all 26Show fewer
  • 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;
  • 8. 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);
  • Low count of white blood cells (leukocytes < 3000/mm3);
  • History of hypersensitivity to isotretinoin and parabens;
  • Alcohol intake;
  • Previous or actual history of rheumatologic diseases;
  • Anticancer chemotherapy in the last 3 months;
  • Previous history of hypervitaminosis A;
  • Previous history of bone or muscular diseases;
  • 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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site
  • Dermatology Outpatient Clinic - Hospital das Clínicas - Federal University of Goias (UFG)

    Goiânia, Goiás, 74605-020

Other trials in Brazil

About this study

Official title: Low Dose Oral Isotretinoin Versus Topical Tretinoin for Prevention of Actinic Keratosis in Immunocompetent Patients: a Randomized, Comparative Trial

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.

Read the 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.

Being tested
Oral isotretinoin, Tretinoin 0,05% cream, Sunscreen FPS 60
Keywords
actinic keratosis, tretinoin, isotretinoin, cryotherapy, sun protection factor, clinical clearance
Medical subject headings
Keratosis, Actinic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral isotretinoinDrug

    Also called Acnova

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

  • Tretinoin 0,05% creamDrug

    Also called Vitacid 0,05% cream

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

  • Sunscreen FPS 60Drug

    Also called Skin Block 60 Fluide Extreme

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

Study groups in NCT02278861
Study groupRoleWhat they receive
Oral isotretinoin 10mg/dayActive comparatorOral 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.
Receives: Drug: Oral isotretinoin; Drug: Sunscreen FPS 60
Tretinoin 0,05% creamActive comparatorAn 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.
Receives: Drug: Tretinoin 0,05% cream; Drug: Sunscreen FPS 60

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

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

Secondary outcomes (5)
  1. Reduction in the thickness of the stratum corneum

    Skin biopsies will be taken from patients at the time of randomization (T120) and after the treatment with retinoids (T300) and stained with hematoxilin-eosin (HE)

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

  2. Increase in the epithelium thickness

    Skin biopsies will be taken from patients at the time of randomization (T120) and after the treatment with retinoids (T300) and stained with hematoxilin-eosin (HE)

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

  3. Reduction in the expression of p53 protein

    Skin biopsies will be taken from patients at the time of randomization (T120) and after the treatment with retinoids (T300). Retinoids are known to reduce the expression of this marker of carcinogenesis.

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

  4. Reduction in the expression of the Bcl-2 protein

    Skin biopsies will be taken from patients at the time of randomization (T120) and after the treatment with retinoids (T300). Retinoids are known to reduce the expression of this marker of carcinogenesis.

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

  5. Increase in the expression of Bax protein

    Skin biopsies will be taken from patients at the time of randomization (T120) and after the treatment with retinoids (T300). Retinoids are known to increase the expression of this marker of carcinogenesis.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2014 (estimated)
  2. Study startNov 2011
  3. Primary completionApr 2014
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02278861
Sponsor's protocol ID
UFG 133/11
Acronym
ARISOAK
Status last verified
Oct 2014
First submitted
28 Oct 2014
Last updated
30 Oct 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24068130
  • 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.

    PubMed 11493098

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral isotretinoin, Tretinoin 0,05% cream and Sunscreen FPS 60 in people with Actinic Keratosis, run by Universidade Federal de Goias at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction in the counting of actinic keratosis in the face and forearms (time frame: at the beginning (T0), 120 days (T120) and 300 days (T300)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02278861, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2014.

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