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

NCT01407471 | Completed Phase 2

• 1 other identifier: P071011
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cutaneous Atrophy Due to Corticosteroids

Keywords

aldosterone; clobetasol; atrophy; skin; epidermis; wound healing; mineral corticoid receptor; spironolactone

Outcome Measures

Primary Outcomes (1)

• histological measure of epidermal thickness

  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.

  day 29

Secondary Outcomes (3)

• delay of healing after skin biopsies performed on day 29

  days 32, 36, 39, 43, 46, 50

• Dermis thickness evaluated by ultrasound

  days 1, 15, 29

• Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry

  day 29

Study Arms (4)

Clobetasol + Spironolactone

EXPERIMENTAL

0.05% clobetasol and 5% spironolactone

Drug: Clobetasol + Spironolactone

Clobetasol + Placebo

ACTIVE COMPARATOR

0.05% clobetasol + inert excipient

Drug: Clobetasol + Placebo

Placebo + Spironolactone

ACTIVE COMPARATOR

Inert excipient + 5% spironolactone

Drug: Placebo + Spironolactone

Placebo + placebo

PLACEBO COMPARATOR

Inert excipient

Drug: Placebo + Placebo

Interventions

Clobetasol + Spironolactone DRUG

One application 6 days a week during 4 weeks

Clobetasol + Spironolactone

Clobetasol + Placebo DRUG

One application 6 days a week during 4 weeks

Clobetasol + Placebo

Placebo + Spironolactone DRUG

One application 6 days a week during 7 weeks

Placebo + Spironolactone

Placebo + Placebo DRUG

One application 6 days a week during 7 weeks

Placebo + placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers of both sex, aged between 20 and 50 years
• 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

You may not qualify if:

• Chronic Alcoholism
• Drug-addiction (comprehensive interview with a sampling in case of doubt)
• Woman pregnant or breast-feeding
• 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 ...)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Société de Dermatologie Française: collaborator

Study Sites (1)

Bichat Hospital

Paris, 75877, France

Location

Related Publications (13)

• 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.

  PMID: 19925636 BACKGROUND

• 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.

  PMID: 18039792 BACKGROUND

• 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.

  PMID: 17675581 BACKGROUND

• 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.

  PMID: 17095510 BACKGROUND

• 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.

  PMID: 16061697 BACKGROUND

• 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.

  PMID: 12032844 BACKGROUND

• 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.

  PMID: 11918703 BACKGROUND

• 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.

  PMID: 11511512 BACKGROUND

• 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.

  PMID: 10504339 BACKGROUND

• 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.

  PMID: 8838661 BACKGROUND

• 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.

  PMID: 7962326 BACKGROUND

• 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.

  PMID: 2147469 BACKGROUND

• 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.

  PMID: 25668238 BACKGROUND

MeSH Terms

Conditions

Atrophy

Interventions

Clobetasol; Spironolactone

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Betamethasone; Steroids, Fluorinated; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Lactones; Organic Chemicals; Pregnenes; Pregnanes

Study Officials

• Eve MAUBEC, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: August 2, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: July 3, 2015

Record last verified: 2015-02

Locations

FR (1)