Skin bioMARkers for Atopic Eczema Therapy Evaluation

Summary

The study aims to investigate two new non-invasive technologies for assessing skin properties to identify and validate a range of safety biomarkers that may be considered useful as primary outcome measures for evaluating the safety of topical treatments in atopic dermatitis. The method of assessing these biomarker technologies will be to determine whether twice daily treatment with crisaborole (2%) ointment, compared to betamethasone valerate (0.1%) cream, for up to 4 weeks, may cause skin structure or function changes, like skin atrophy, in patients with atopic dermatitis (AD).

Timeline

Start

2020-11-20

Primary completion

2021-09-30

Completion

2021-09-30

Publications

• Background Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI; ISAAC Phase Three Study Group. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009 Dec;124(6):1251-8.e23. doi: 10.1016/j.jaci.2009.10.009.
• Background Kerr OA, Tidman MJ, Walker JJ, Aldridge RD, Benton EC. The profile of dermatological problems in primary care. Clin Exp Dermatol. 2010 Jun;35(4):380-3. doi: 10.1111/j.1365-2230.2009.03586.x. Epub 2009 Oct 23.
• Background Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, Macgowan AL, Tazi-Ahnini R, Ward SJ. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol. 2009 Aug;129(8):1892-908. doi: 10.1038/jid.2009.133. Epub 2009 Jun 4.
• Background Punekar YS, Sheikh A. Establishing the sequential progression of multiple allergic diagnoses in a UK birth cohort using the General Practice Research Database. Clin Exp Allergy. 2009 Dec;39(12):1889-95. doi: 10.1111/j.1365-2222.2009.03366.x. Epub 2009 Oct 7.
• Background Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy. 2004 Apr;34(4):520-6. doi: 10.1111/j.1365-2222.2004.1935.x.
• Background Lewis-Jones S, Mugglestone MA; Guideline Development Group. Management of atopic eczema in children aged up to 12 years: summary of NICE guidance. BMJ. 2007 Dec 15;335(7632):1263-4. doi: 10.1136/bmj.39405.503773.AD. No abstract available.
• Background Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006 Jan;54(1):1-15; quiz 16-8. doi: 10.1016/j.jaad.2005.01.010.
• Background Schmitt J, von Kobyletzki L, Svensson A, Apfelbacher C. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2011 Feb;164(2):415-28. doi: 10.1111/j.1365-2133.2010.10030.x. Epub 2010 Nov 23.
• Background Batchelor JM, Ridd MJ, Clarke T, Ahmed A, Cox M, Crowe S, Howard M, Lawton S, McPhee M, Rani A, Ravenscroft JC, Roberts A, Thomas KS. The Eczema Priority Setting Partnership: a collaboration between patients, carers, clinicians and researchers to identify and prioritize important research questions for the treatment of eczema. Br J Dermatol. 2013 Mar;168(3):577-82. doi: 10.1111/bjd.12040. Epub 2013 Jan 18.
• Background Byers RA, Maiti R, Danby SG, Pang EJ, Mitchell B, Carre MJ, Lewis R, Cork MJ, Matcher SJ. Sub-clinical assessment of atopic dermatitis severity using angiographic optical coherence tomography. Biomed Opt Express. 2018 Mar 29;9(4):2001-2017. doi: 10.1364/BOE.9.002001. eCollection 2018 Apr 1.
• Background Ugryumova N, Jacobs J, Bonesi M, Matcher SJ. Novel optical imaging technique to determine the 3-D orientation of collagen fibers in cartilage: variable-incidence angle polarization-sensitive optical coherence tomography. Osteoarthritis Cartilage. 2009 Jan;17(1):33-42. doi: 10.1016/j.joca.2008.05.005. Epub 2008 Jul 14.
• Background Danby SG, Brown K, Higgs-Bayliss T, Chittock J, Albenali L, Cork MJ. The Effect of an Emollient Containing Urea, Ceramide NP, and Lactate on Skin Barrier Structure and Function in Older People with Dry Skin. Skin Pharmacol Physiol. 2016;29(3):135-47. doi: 10.1159/000445955. Epub 2016 Jun 2.
• Background Boncheva M, Damien F, Normand V. Molecular organization of the lipid matrix in intact Stratum corneum using ATR-FTIR spectroscopy. Biochim Biophys Acta. 2008 May;1778(5):1344-55. doi: 10.1016/j.bbamem.2008.01.022. Epub 2008 Feb 11.
• Background Damien F, Boncheva M. The extent of orthorhombic lipid phases in the stratum corneum determines the barrier efficiency of human skin in vivo. J Invest Dermatol. 2010 Feb;130(2):611-4. doi: 10.1038/jid.2009.272. Epub 2009 Sep 3. No abstract available.
• Background Chittock J, Brown K, Cork MJ, Danby SG. Comparing the Effect of a Twice-weekly Tacrolimus and Betamethasone Valerate Dose on the Subclinical Epidermal Barrier Defect in Atopic Dermatitis. Acta Derm Venereol. 2015 Jul;95(6):653-8. doi: 10.2340/00015555-2048.
• Background Danby SG, Chittock J, Brown K, Albenali LH, Cork MJ. The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis. Br J Dermatol. 2014 Apr;170(4):914-21. doi: 10.1111/bjd.12778.
• Background Kezic S, O'Regan GM, Yau N, Sandilands A, Chen H, Campbell LE, Kroboth K, Watson R, Rowland M, McLean WH, Irvine AD. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy. 2011 Jul;66(7):934-40. doi: 10.1111/j.1398-9995.2010.02540.x. Epub 2011 Jan 25.
• Background Lu Z, Kasaragod D, Matcher SJ. Conical scan polarization-sensitive optical coherence tomography. Biomed Opt Express. 2014 Feb 18;5(3):752-62. doi: 10.1364/BOE.5.000752. eCollection 2014 Mar 1.
• Background Chittock J, Cooke A, Lavender T, Brown K, Wigley A, Victor S, Cork MJ, Danby SG. Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults. Br J Dermatol. 2016 Oct;175(4):713-20. doi: 10.1111/bjd.14568. Epub 2016 Jul 22.
• Background Danby SG, AlEnezi T, Sultan A, Lavender T, Chittock J, Brown K, Cork MJ. Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care. Pediatr Dermatol. 2013 Jan-Feb;30(1):42-50. doi: 10.1111/j.1525-1470.2012.01865.x. Epub 2012 Sep 20.
• Background Brancaleon L, Bamberg MP, Sakamaki T, Kollias N. Attenuated total reflection-Fourier transform infrared spectroscopy as a possible method to investigate biophysical parameters of stratum corneum in vivo. J Invest Dermatol. 2001 Mar;116(3):380-6. doi: 10.1046/j.1523-1747.2001.01262.x.
• Background Ring A, Schreiner V, Wenck H, Wittern KP, Kupper L, Keyhani R. Mid-infrared spectroscopy on skin using a silver halide fibre probe in vivo. Skin Res Technol. 2006 Feb;12(1):18-23. doi: 10.1111/j.0909-725X.2006.00130.x.
• Background Cooke A, Cork MJ, Victor S, Campbell M, Danby S, Chittock J, Lavender T. Olive Oil, Sunflower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study). Acta Derm Venereol. 2016 Mar;96(3):323-30. doi: 10.2340/00015555-2279.
• Background Kao JS, Fluhr JW, Man MQ, Fowler AJ, Hachem JP, Crumrine D, Ahn SK, Brown BE, Elias PM, Feingold KR. Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities. J Invest Dermatol. 2003 Mar;120(3):456-64. doi: 10.1046/j.1523-1747.2003.12053.x.

Drugs

Indications