Clinical trial NCT01407471: Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy
Official title: Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous Atrophy Due to Corticosteroids
Keywords: aldosterone
clobetasol
atrophy
skin
epidermis
wound healing
mineral corticoid receptor
spironolactone
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Société de Dermatologie Française
First posted: 2011-08-02
Enrollment: 26
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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

Detailed 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.

Eligibility criteria: 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 ...)

Primary outcomes:
measure: histological measure of epidermal thickness
timeFrame: day 29
Secondary outcomes:
measure: delay of healing after skin biopsies performed on day 29
timeFrame: days 32, 36, 39, 43, 46, 50
measure: Dermis thickness evaluated by ultrasound
timeFrame: days 1, 15, 29
measure: Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry
timeFrame: day 29
Other outcomes:
Locations:
city: Paris
country: France
facility: Bichat Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Eve MAUBEC, MD
role: PRINCIPAL_INVESTIGATOR
References:
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