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

Primary Purpose

Cutaneous Atrophy Due to Corticosteroids

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Clobetasol + Spironolactone
Clobetasol + Placebo
Placebo + Spironolactone
Placebo + Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cutaneous Atrophy Due to Corticosteroids focused on measuring aldosterone, clobetasol, atrophy, skin, epidermis, wound healing, mineral corticoid receptor, spironolactone

Eligibility Criteria

20 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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 ...)

Sites / Locations

  • Bichat Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Clobetasol + Spironolactone

Clobetasol + Placebo

Placebo + Spironolactone

Placebo + placebo

Arm Description

0.05% clobetasol and 5% spironolactone

0.05% clobetasol + inert excipient

Inert excipient + 5% spironolactone

Inert excipient

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

delay of healing after skin biopsies performed on day 29
Dermis thickness evaluated by ultrasound
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry

Full Information

First Posted
June 30, 2011
Last Updated
July 2, 2015
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Société de Dermatologie Française
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1. Study Identification

Unique Protocol Identification Number
NCT01407471
Brief Title
Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy
Acronym
SPIREPI
Official Title
Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Société de Dermatologie Française

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous Atrophy Due to Corticosteroids
Keywords
aldosterone, clobetasol, atrophy, skin, epidermis, wound healing, mineral corticoid receptor, spironolactone

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clobetasol + Spironolactone
Arm Type
Experimental
Arm Description
0.05% clobetasol and 5% spironolactone
Arm Title
Clobetasol + Placebo
Arm Type
Active Comparator
Arm Description
0.05% clobetasol + inert excipient
Arm Title
Placebo + Spironolactone
Arm Type
Active Comparator
Arm Description
Inert excipient + 5% spironolactone
Arm Title
Placebo + placebo
Arm Type
Placebo Comparator
Arm Description
Inert excipient
Intervention Type
Drug
Intervention Name(s)
Clobetasol + Spironolactone
Intervention Description
One application 6 days a week during 4 weeks
Intervention Type
Drug
Intervention Name(s)
Clobetasol + Placebo
Intervention Description
One application 6 days a week during 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo + Spironolactone
Intervention Description
One application 6 days a week during 7 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo + Placebo
Intervention Description
One application 6 days a week during 7 weeks
Primary Outcome Measure Information:
Title
histological measure of epidermal thickness
Description
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.
Time Frame
day 29
Secondary Outcome Measure Information:
Title
delay of healing after skin biopsies performed on day 29
Time Frame
days 32, 36, 39, 43, 46, 50
Title
Dermis thickness evaluated by ultrasound
Time Frame
days 1, 15, 29
Title
Mineral receptors and glucoreceptors expression ratio performed by immunohistochemistry
Time Frame
day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 ...)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eve MAUBEC, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bichat Hospital
City
Paris
ZIP/Postal Code
75877
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
19925636
Citation
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Results Reference
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PubMed Identifier
18039792
Citation
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.
Results Reference
background
PubMed Identifier
17675581
Citation
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.
Results Reference
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PubMed Identifier
17095510
Citation
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Results Reference
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PubMed Identifier
16061697
Citation
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.
Results Reference
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PubMed Identifier
12032844
Citation
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PubMed Identifier
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Citation
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Citation
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PubMed Identifier
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Citation
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Citation
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Citation
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Results Reference
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Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy

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