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

Information source: Assistance Publique - Hôpitaux de Paris
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cutaneous Atrophy Due to Corticosteroids

Intervention: Clobetasol + Spironolactone (Drug); Clobetasol + Placebo (Drug); Placebo + Spironolactone (Drug); Placebo + Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Eve MAUBEC, MD, Principal Investigator, Affiliation: Assistance Publique - HĂ´pitaux de Paris

Overall contact:
Valérie VIGNALI, technician, Phone: 01 40 25 71 45, Email: valerie.vignali@bch.aphp.fr

Summary

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

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: histological measure of epidermal thickness

Secondary outcome:

delay of healing after skin biopsies performed on day 29

Dermis thickness evaluated by ultrasound

Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry

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

Minimum age: 20 Years. Maximum age: 50 Years. Gender(s): Both.

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 ...)

Locations and Contacts

Valérie VIGNALI, technician, Phone: 01 40 25 71 45, Email: valerie.vignali@bch.aphp.fr

Bichat Hospital, Paris 75877, France; Recruiting
Additional Information

Related publications:

Farman N, Maubec E, Poeggeler B, Klatte JE, Jaisser F, Paus R. The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon? Exp Dermatol. 2010 Feb;19(2):100-7. Epub 2009 Nov 18. Review.

Bayo P, Sanchis A, Bravo A, Cascallana JL, Buder K, Tuckermann J, SchĂĽtz G, PĂ©rez P. Glucocorticoid receptor is required for skin barrier competence. Endocrinology. 2008 Mar;149(3):1377-88. Epub 2007 Nov 26.

Sainte Marie Y, Toulon A, Paus R, Maubec E, Cherfa A, Grossin M, Descamps V, Clemessy M, Gasc JM, Peuchmaur M, Glick A, Farman N, Jaisser F. Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia. Am J Pathol. 2007 Sep;171(3):846-60. Epub 2007 Aug 3.

Stojadinovic O, Lee B, Vouthounis C, Vukelic S, Pastar I, Blumenberg M, Brem H, Tomic-Canic M. Novel genomic effects of glucocorticoids in epidermal keratinocytes: inhibition of apoptosis, interferon-gamma pathway, and wound healing along with promotion of terminal differentiation. J Biol Chem. 2007 Feb 9;282(6):4021-34. Epub 2006 Nov 9.

Leyvraz C, Charles RP, Rubera I, Guitard M, Rotman S, Breiden B, Sandhoff K, Hummler E. The epidermal barrier function is dependent on the serine protease CAP1/Prss8. J Cell Biol. 2005 Aug 1;170(3):487-96.

List K, Haudenschild CC, Szabo R, Chen W, Wahl SM, Swaim W, Engelholm LH, Behrendt N, Bugge TH. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene. 2002 May 23;21(23):3765-79.

Mauro T, Guitard M, Behne M, Oda Y, Crumrine D, Komuves L, Rassner U, Elias PM, Hummler E. The ENaC channel is required for normal epidermal differentiation. J Invest Dermatol. 2002 Apr;118(4):589-94.

Pérez P, Page A, Bravo A, Del Río M, Giménez-Conti I, Budunova I, Slaga TJ, Jorcano JL. Altered skin development and impaired proliferative and inflammatory responses in transgenic mice overexpressing the glucocorticoid receptor. FASEB J. 2001 Sep;15(11):2030-2. Epub 2001 Jul 24.

Brouard M, Casado M, Djelidi S, Barrandon Y, Farman N. Epithelial sodium channel in human epidermal keratinocytes: expression of its subunits and relation to sodium transport and differentiation. J Cell Sci. 1999 Oct;112 ( Pt 19):3343-52.

Roudier-Pujol C, Rochat A, Escoubet B, Eugène E, Barrandon Y, Bonvalet JP, Farman N. Differential expression of epithelial sodium channel subunit mRNAs in rat skin. J Cell Sci. 1996 Feb;109 ( Pt 2):379-85.

Kenouch S, Lombes M, Delahaye F, Eugene E, Bonvalet JP, Farman N. Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab. 1994 Nov;79(5):1334-41.

Messina M, Manieri C, Musso MC, Pastorino R. Oral and topical spironolactone therapies in skin androgenization. Panminerva Med. 1990 Apr-Jun;32(2):49-55.

Starting date: September 2011
Last updated: September 20, 2011

Page last updated: December 08, 2011

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