Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy (SPIREPI)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 2

Conditions: Cutaneous Atrophy Due to Corticosteroids

Treatments: Drug: Clobetasol + Spironolactone; Drug: Clobetasol + Placebo; Drug: Placebo + Placebo; Drug: Placebo + Spironolactone

Study type: Interventional

Funder types: Other

Identifiers

NCT01407471

P071011

Details and patient eligibility

About

The purpose of this study is to determine whether spironolactone could significantly reduce cutaneous atrophy due to corticosteroids.

Full description

skin cutaneous atrophy due to corticosteroids limits the long-term use of highly potent topical glucocorticoids which are the treatment of choice for many inflammatory skin diseases. This atrophy results in fragile skin, delay of healing, purpura, irreversible striae, telangiectasia and secondary infections. Up to now, no treatments can prevent efficiently skin atrophy.

The mineralocorticoid receptor, belonging to the superfamily of nuclear receptors, is expressed in human epidermis but its actual function is unknown. Experimental results in animals obtained in INSERM unit U772 by Dr N FARMAN suggest that spironolactone which is a mineralocorticoid receptor antagonist 1- might limit epidermal atrophy and 2- might promote healing.

Study description We propose to test clinically these hypotheses for the first time on humans, at the CIC in BICHAT's hospital on healthy volunteers: 1- by applying on the skin a highly potent cutaneous corticosteroids in association or not with spironolactone, 2- by applying or not spironolactone on wounds after 3-mm punch biopsies.

Enrollment: 26 patients

Sex: All

Ages: 20 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteers of both sex, aged between 20 and 50 years
• Woman with effective contraception and pregnancy test negative before inclusion.
• Subject considered healthy after a detailed review (interview, clinical examination)
• Subject belonging to a social security scheme (beneficiary or have the right)
• Subject having signed a free and informed consent
• Integrity of the skin at forearms
• Subject available the next 7 weeks and able to go to CIC once a day from Monday to Friday
• Subject accepting four skin biopsies at D29
• no washing forearms during 2 hours after applications

Exclusion criteria

• Chronic Alcoholism
• Drug-addiction (comprehensive interview with a sampling in case of doubt)
• Woman pregnant or breast-feeding
• Subject involved in another trial or in exclusion period of another protocol
• Subject has already received more than 3700 Euros in compensation for damages suffered constraints in the past 12 months for his involvement in biomedical researches
• Subject has already participated in this protocol
• Phototypes 5 and 6
• Clinical skin atrophy
• History of severe chronic skin disease
• Problems of healing
• Treatment with oral corticosteroids, mineralocorticoids or spironolactone (Aldactone, Flumach, Practon, Spiroctan, Spironone, Aldactazine, ALDALIX, Practazin, Spiroctazine ...)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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26 participants in 4 patient groups, including a placebo group

Clobetasol + Spironolactone

Experimental group

Description:

0.05% clobetasol and 5% spironolactone

Treatment:

Drug: Clobetasol + Spironolactone

Clobetasol + Placebo

Active Comparator group

Description:

0.05% clobetasol + inert excipient

Treatment:

Drug: Clobetasol + Placebo

Placebo + Spironolactone

Active Comparator group

Description:

Inert excipient + 5% spironolactone

Treatment:

Drug: Placebo + Spironolactone

Placebo + placebo

Placebo Comparator group

Description:

Inert excipient

Treatment:

Drug: Placebo + Placebo