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

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

Detailed Description
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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.

Official Title
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Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy

Conditions
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Cutaneous Atrophy Due to Corticosteroids

Intervention / Treatment
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* Drug: Clobetasol + Spironolactone
* Drug: Clobetasol + Placebo
* Drug: Placebo + Spironolactone
* Drug: Placebo + Placebo


Participation Criteria
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Eligibility Criteria
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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 ...)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clobetasol + Spironolactone<br>0.05% clobetasol and 5% spironolactone | Drug: Clobetasol + Spironolactone<br>* One application 6 days a week during 4 weeks<br>|
| Active Comparator: Clobetasol + Placebo<br>0.05% clobetasol + inert excipient | Drug: Clobetasol + Placebo<br>* One application 6 days a week during 4 weeks<br>|
| Active Comparator: Placebo + Spironolactone<br>Inert excipient + 5% spironolactone | Drug: Placebo + Spironolactone<br>* One application 6 days a week during 7 weeks<br>|
| Placebo Comparator: Placebo + placebo<br>Inert excipient | Drug: Placebo + Placebo<br>* One application 6 days a week during 7 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| histological measure of epidermal thickness | biopsies will be performed in the center of the treated sites. Epidermal thickness will be measured from the basal lamina to the lower border of the stratum corneum. This will be determined by image analysis from the average of fields per skin section. | day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delay of healing after skin biopsies performed on day 29 |  | days 32, 36, 39, 43, 46, 50 | 
| Dermis thickness evaluated by ultrasound |  | days 1, 15, 29 | 
| Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry |  | day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aldosterone, clobetasol, atrophy, skin, epidermis, wound healing, mineral corticoid receptor, spironolactone