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

Phase 2
Completed
Conditions
Cutaneous Atrophy Due to Corticosteroids
Interventions
Registration Number
NCT01407471
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
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 ...)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Placebo + SpironolactonePlacebo + SpironolactoneInert excipient + 5% spironolactone
Placebo + placeboPlacebo + PlaceboInert excipient
Clobetasol + SpironolactoneClobetasol + Spironolactone0.05% clobetasol and 5% spironolactone
Clobetasol + PlaceboClobetasol + Placebo0.05% clobetasol + inert excipient
Primary Outcome Measures
NameTimeMethod
histological measure of epidermal thicknessday 29

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.

Secondary Outcome Measures
NameTimeMethod
Dermis thickness evaluated by ultrasounddays 1, 15, 29
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistryday 29
delay of healing after skin biopsies performed on day 29days 32, 36, 39, 43, 46, 50

Trial Locations

Locations (1)

Bichat Hospital

🇫🇷

Paris, France

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