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

NCT ID: NCT01407471

Last Updated: 2015-07-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-30

Study Completion Date

2012-05-31

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.

Conditions

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Cutaneous Atrophy Due to Corticosteroids

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Clobetasol + Spironolactone

0.05% clobetasol and 5% spironolactone

Group Type EXPERIMENTAL

Clobetasol + Spironolactone

Intervention Type DRUG

One application 6 days a week during 4 weeks

Clobetasol + Placebo

0.05% clobetasol + inert excipient

Group Type ACTIVE_COMPARATOR

Clobetasol + Placebo

Intervention Type DRUG

One application 6 days a week during 4 weeks

Placebo + Spironolactone

Inert excipient + 5% spironolactone

Group Type ACTIVE_COMPARATOR

Placebo + Spironolactone

Intervention Type DRUG

One application 6 days a week during 7 weeks

Placebo + placebo

Inert excipient

Group Type PLACEBO_COMPARATOR

Placebo + Placebo

Intervention Type DRUG

One application 6 days a week during 7 weeks

Interventions

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Clobetasol + Spironolactone

One application 6 days a week during 4 weeks

Intervention Type DRUG

Clobetasol + Placebo

One application 6 days a week during 4 weeks

Intervention Type DRUG

Placebo + Spironolactone

One application 6 days a week during 7 weeks

Intervention Type DRUG

Placebo + Placebo

One application 6 days a week during 7 weeks

Intervention Type DRUG

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 ...)
Minimum Eligible Age

20 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Société de Dermatologie Française

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eve MAUBEC, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Bichat Hospital

Paris, , France

Site Status

Countries

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France

References

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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. doi: 10.1111/j.1600-0625.2009.01011.x. Epub 2009 Nov 18.

Reference Type BACKGROUND
PMID: 19925636 (View on PubMed)

Bayo P, Sanchis A, Bravo A, Cascallana JL, Buder K, Tuckermann J, Schutz G, Perez P. Glucocorticoid receptor is required for skin barrier competence. Endocrinology. 2008 Mar;149(3):1377-88. doi: 10.1210/en.2007-0814. Epub 2007 Nov 26.

Reference Type BACKGROUND
PMID: 18039792 (View on PubMed)

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. doi: 10.2353/ajpath.2007.060991. Epub 2007 Aug 3.

Reference Type BACKGROUND
PMID: 17675581 (View on PubMed)

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. doi: 10.1074/jbc.M606262200. Epub 2006 Nov 9.

Reference Type BACKGROUND
PMID: 17095510 (View on PubMed)

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. doi: 10.1083/jcb.200501038.

Reference Type BACKGROUND
PMID: 16061697 (View on PubMed)

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. doi: 10.1038/sj.onc.1205502.

Reference Type BACKGROUND
PMID: 12032844 (View on PubMed)

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. doi: 10.1046/j.1523-1747.2002.01721.x.

Reference Type BACKGROUND
PMID: 11918703 (View on PubMed)

Perez P, Page A, Bravo A, Del Rio M, Gimenez-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. doi: 10.1096/fj.00-0772fje. Epub 2001 Jul 24.

Reference Type BACKGROUND
PMID: 11511512 (View on PubMed)

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. doi: 10.1242/jcs.112.19.3343.

Reference Type BACKGROUND
PMID: 10504339 (View on PubMed)

Roudier-Pujol C, Rochat A, Escoubet B, Eugene 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. doi: 10.1242/jcs.109.2.379.

Reference Type BACKGROUND
PMID: 8838661 (View on PubMed)

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. doi: 10.1210/jcem.79.5.7962326.

Reference Type BACKGROUND
PMID: 7962326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2147469 (View on PubMed)

Maubec E, Laouenan C, Deschamps L, Nguyen VT, Scheer-Senyarich I, Wackenheim-Jacobs AC, Steff M, Duhamel S, Tubiana S, Brahimi N, Leclerc-Mercier S, Crickx B, Perret C, Aractingi S, Escoubet B, Duval X, Arnaud P, Jaisser F, Mentre F, Farman N. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin. J Invest Dermatol. 2015 Jul;135(7):1781-1789. doi: 10.1038/jid.2015.44. Epub 2015 Feb 10.

Reference Type BACKGROUND
PMID: 25668238 (View on PubMed)

Other Identifiers

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P071011

Identifier Type: -

Identifier Source: org_study_id

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