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

Purpose

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

Condition	Intervention	Phase
Cutaneous Atrophy Due to Corticosteroids	Drug: Clobetasol + Spironolactone Drug: Clobetasol + Placebo Drug: Placebo + Spironolactone Drug: Placebo + Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy

Resource links provided by NLM:

MedlinePlus related topics: Minerals Steroids

Drug Information available for: Spironolactone Clobetasol propionate

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

histological measure of epidermal thickness [ Time Frame: day 29 ] [ Designated as safety issue: No ]
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:

delay of healing after skin biopsies performed on day 29 [ Time Frame: days 32, 36, 39, 43, 46, 50 ] [ Designated as safety issue: No ]
Dermis thickness evaluated by ultrasound [ Time Frame: days 1, 15, 29 ] [ Designated as safety issue: No ]
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry [ Time Frame: day 29 ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	September 2011
Study Completion Date:	May 2012
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Clobetasol + Spironolactone 0.05% clobetasol and 5% spironolactone	Drug: Clobetasol + Spironolactone One application 6 days a week during 4 weeks Other Name: Clobetasol + Spironolactone
Active Comparator: Clobetasol + Placebo 0.05% clobetasol + inert excipient	Drug: Clobetasol + Placebo One application 6 days a week during 4 weeks Other Name: Clobetasol + Placebo
Active Comparator: Placebo + Spironolactone Inert excipient + 5% spironolactone	Drug: Placebo + Spironolactone One application 6 days a week during 7 weeks Other Name: Placebo + Spironolactone
Placebo Comparator: Placebo + placebo Inert excipient	Drug: Placebo + Placebo One application 6 days a week during 7 weeks Other Name: Placebo + Placebo

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

Ages Eligible for Study:	20 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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 ...)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407471

Locations

France
Bichat Hospital
Paris, France, 75877

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Société de Dermatologie Française

Investigators

Principal Investigator:

Eve MAUBEC, MD

Assistance Publique - Hôpitaux de Paris

More Information

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, Schütz G, Pérez 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.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01407471 History of Changes
Other Study ID Numbers:	P071011
Study First Received:	June 30, 2011
Last Updated:	May 14, 2012
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

aldosterone
clobetasol
atrophy
skin

epidermis
wound healing
mineral corticoid receptor
spironolactone

Additional relevant MeSH terms:

Atrophy
Pathological Conditions, Anatomical
Clobetasol
Spironolactone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Aldosterone Antagonists
Hormone Antagonists
Diuretics
Natriuretic Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on June 18, 2013

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