Cutaneous Atrophy Due to CorticosteroidsPhase 2SPIREPINCT01407471

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

A Phase 2 study testing Clobetasol + Spironolactone in people with Cutaneous Atrophy Due to Corticosteroids, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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

Who is it for?: Ages 20 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Cutaneous Atrophy Due to Corticosteroids
What is being tested?: Clobetasol + Spironolactone
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteFrance
Study dates: Sep 2011to May 2012
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Show all 9Show fewer

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

Who cannot join

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

Show all 11Show fewer

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 ...)

Trial locations and contacts

1 site in 1 country.

France1 site

Bichat Hospital
Paris, 75877

Other trials in France

About this study

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

Read the 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.

Conditions: Cutaneous Atrophy Due to Corticosteroids
Being tested: Clobetasol + Spironolactone, Clobetasol + Placebo, Placebo + Spironolactone, Placebo + Placebo
Keywords: aldosterone, clobetasol, atrophy, skin, epidermis, wound healing, mineral corticoid receptor, spironolactone
Medical subject headings: Atrophy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Clobetasol + SpironolactoneDrug
One application 6 days a week during 4 weeks
Clobetasol + PlaceboDrug
One application 6 days a week during 4 weeks
Placebo + SpironolactoneDrug
One application 6 days a week during 7 weeks
Placebo + PlaceboDrug
One application 6 days a week during 7 weeks

Study groups in NCT01407471
Study group	Role	What they receive
Clobetasol + Spironolactone	Experimental	0.05% clobetasol and 5% spironolactone Receives: Drug: Clobetasol + Spironolactone
Clobetasol + Placebo	Active comparator	0.05% clobetasol + inert excipient Receives: Drug: Clobetasol + Placebo
Placebo + Spironolactone	Active comparator	Inert excipient + 5% spironolactone Receives: Drug: Placebo + Spironolactone
Placebo + placebo	Placebo comparator	Inert excipient Receives: Drug: Placebo + Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: day 29

Secondary outcomes (3)

delay of healing after skin biopsies performed on day 29
Measured: days 32, 36, 39, 43, 46, 50
Dermis thickness evaluated by ultrasound
Measured: days 1, 15, 29
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry
Measured: day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011May 2012

First posted2 Aug 2011 (estimated)
Study startSep 2011
Primary completionMay 2012
Study completionMay 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Cutaneous Atrophy Due to CorticosteroidsStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01407471
Sponsor's protocol ID: P071011
Acronym: SPIREPI
Status last verified: Feb 2015
First submitted: 30 Jun 2011
Last updated: 3 Jul 2015
Results posted: No
Data monitoring committee: No

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. doi: 10.1111/j.1600-0625.2009.01011.x. Epub 2009 Nov 18.
PubMed 19925636
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.
PubMed 18039792
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.
PubMed 17675581
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.
PubMed 17095510
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.
PubMed 16061697
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.
PubMed 12032844
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.
PubMed 11918703
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.
PubMed 11511512
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.
PubMed 10504339
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.
PubMed 8838661
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.
PubMed 7962326
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.
PubMed 2147469
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.
PubMed 25668238

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy
ClinicalTrials.gov ID: NCT01407471
Acronym / sponsor ID: SPIREPI / P071011
Conditions: Cutaneous Atrophy Due to Corticosteroids
Keywords: aldosterone, clobetasol, atrophy, skin, epidermis, wound healing, mineral corticoid receptor, spironolactone
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Collaborators: Société de Dermatologie Française
Study start: Sep 2011
Primary completion: May 2012 (actual)
Study completion: May 2012 (actual)
First posted: 2 Aug 2011 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Clobetasol + Spironolactone	Experimental	Drug: Clobetasol + Spironolactone0.05% clobetasol and 5% spironolactone
Clobetasol + Placebo	Active comparator	Drug: Clobetasol + Placebo0.05% clobetasol + inert excipient
Placebo + Spironolactone	Active comparator	Drug: Placebo + SpironolactoneInert excipient + 5% spironolactone
Placebo + placebo	Placebo comparator	Drug: Placebo + PlaceboInert excipient

Who may qualify

Ages: 20 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Clobetasol + SpironolactoneOne application 6 days a week during 4 weeks	Drug	Clobetasol + Spironolactone
Clobetasol + PlaceboOne application 6 days a week during 4 weeks	Drug	Clobetasol + Placebo
Placebo + SpironolactoneOne application 6 days a week during 7 weeks	Drug	Placebo + Spironolactone
Placebo + PlaceboOne application 6 days a week during 7 weeks	Drug	Placebo + placebo

Primary outcome

histological measure of epidermal thickness
Time frame: day 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.

3 secondary outcomes

delay of healing after skin biopsies performed on day 29
Time frame: days 32, 36, 39, 43, 46, 50
Dermis thickness evaluated by ultrasound
Time frame: days 1, 15, 29
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry
Time frame: day 29

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2015.
Background: PubMed 19925636Farman 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.
Background: PubMed 18039792Bayo 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.
Background: PubMed 17675581Sainte 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.
Background: PubMed 17095510Stojadinovic 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.
Background: PubMed 16061697Leyvraz 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.
Background: PubMed 12032844List 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.
Background: PubMed 11918703Mauro 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.
Background: PubMed 11511512Perez 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.
Background: PubMed 10504339Brouard 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.
Background: PubMed 8838661Roudier-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.
Background: PubMed 7962326Kenouch 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.
Background: PubMed 2147469Messina M, Manieri C, Musso MC, Pastorino R. Oral and topical spironolactone therapies in skin androgenization. Panminerva Med. 1990 Apr-Jun;32(2):49-55.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eve MAUBEC, MD principal investigator

Assistance Publique - Hôpitaux de Paris

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clobetasol + Spironolactone in people with Cutaneous Atrophy Due to Corticosteroids, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

histological measure of epidermal thickness (time frame: day 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01407471, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2015.