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Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.
- Source :
-
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology [Ann Allergy Asthma Immunol] 2018 Jun; Vol. 120 (6), pp. 631-640.e11. Date of Electronic Publication: 2018 Mar 19. - Publication Year :
- 2018
-
Abstract
- Background: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems.<br />Objective: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD).<br />Methods: A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated.<br />Results: Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, Pā=ā.02) and lipid (adenosine triphosphate-binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, Pā<ā.01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several T <subscript>H</subscript> 17/T <subscript>H</subscript> 22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers.<br />Conclusion: Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities.<br />Trial Registration: clinicaltrials.gov Identifier: NCT02655679.<br /> (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- ATP-Binding Cassette Transporters genetics
ATP-Binding Cassette Transporters immunology
Administration, Cutaneous
Adult
Biological Transport drug effects
Biological Transport immunology
Dermatitis, Atopic genetics
Dermatitis, Atopic immunology
Dermatitis, Atopic pathology
Double-Blind Method
Epidermis immunology
Epidermis pathology
Female
Filaggrin Proteins
Gene Expression Regulation immunology
Humans
Interleukin-6 genetics
Interleukin-6 immunology
Intermediate Filament Proteins genetics
Intermediate Filament Proteins immunology
Keratin-16 genetics
Keratin-16 immunology
Liver X Receptors genetics
Liver X Receptors immunology
Male
Membrane Proteins genetics
Membrane Proteins immunology
Middle Aged
RNA, Messenger genetics
RNA, Messenger immunology
S100A12 Protein genetics
S100A12 Protein immunology
Severity of Illness Index
Sterol Regulatory Element Binding Protein 1 genetics
Sterol Regulatory Element Binding Protein 1 immunology
Treatment Outcome
Anti-Inflammatory Agents therapeutic use
Dermatitis, Atopic drug therapy
Epidermis drug effects
Immunologic Factors therapeutic use
Liver X Receptors agonists
RNA, Messenger agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1534-4436
- Volume :
- 120
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 29567358
- Full Text :
- https://doi.org/10.1016/j.anai.2018.03.013