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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002643-23 | EudraCT Number | ||
| WI242083-UK [Eucrisa] | Other Grant/Funding Number | Pfizer, Inc. | |
| 269415 | Other Identifier | IRAS |
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| Name | Class |
|---|---|
| University of Sheffield | OTHER |
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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).
The first-line drug treatment for mild-moderate AD are currently topical corticosteroids (TCS) with recognized efficacy. However, their prolonged or inappropriate use, can lead to local adverse effects. Side-effects of topical corticosteroids comprise a variety of skin changes in the sense of skin atrophy thinning of the skin and in some cases development of telangiectasia, spontaneous scars, folliculitis, striae distensae (stretch marks), contact dermatitis, acne or rosacea depending on potency, galenic formulation, patient age and body area to which the medication will be applied, exposure time.
Assessing the safety (local adverse effects) of current or new treatments and new treatment approaches using existing treatments through noninvasively monitor on possible early skin (subclinical) changes associated with the local clinical adverse effects of treatment may be an effective step for an enhanced AD treatment management.
Primary Aim: To further develop and validate two new non-invasive technologies for the assessment of early sub-clinical skin changes associated with adverse effects and to derive an optimum panel of safety biomarkers for use in future clinical trials of topical anti-inflammatory treatments.
The safety of two topical anti-inflammatory treatments for AD will be compared in this clinical trial, with a focus on early sub-clinical signs: crisaborole 2% ointment and betamethasone valerate 0,1% cream. Step 1 involves the collection of data on the early sub-clinical skin changes using the non-invasive technologies: OCT and FTIR spectroscopy. The data from this study will then be used to identify and refine biophysical biomarkers of skin atrophy and skin barrier disruption in steps 2 and 3.
Secondary Aim: To determine the relative local skin effects of crisaborole (2%) ointment compared to a potent and moderately potent TCS in participants with mild to moderate AD. The focus is on 'early biomarkers' of 'local skin changes'and not clinical efficacy, which has been established in previous trials.
Rationale for selecting the two comparators are related to prescription behaviors in UK (Betamethasone valerate 0,1% cream) and with no reported TCS-like local adverse effects profile (crisaborole 2% ointment)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| crisaborole and topical Corticosteroid | Other | crisaborole (2%) ointment on the other forearm, twice daily application for 4 weeks (randomised site allocation) betamethasone valerate (0.1%) cream on one forearm, twice daily application for 4 weeks (randomised site allocation) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| crisaborole (2%) ointment | Drug | twice daily application on one forearm for 4 weeks (randomised site allocation) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Epidermal Thickness | The difference in the change in epidermal thickness, measured by structural OCT, between the sites treated with crisaborole (2%) ointment and betamethasone valerate (0.1%) cream. | Day 1 - Day 57 |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of Change in Objective Erythema | Analysis of the difference in the change in skin redness/erythema (relating to tolerability) during and after 28 days treatment determined by Mexameter measured on day 1, day 15, day 29 and day 57. The Mexameter device has a range of 0-999AU (arbitrary units) and the lower the value, the better the condition of the skin. Objective redness can be classified using the following scale: 0-170AU - No erythema; 170-330AU - Minimal erythema; 330-450AU - Diffuse erythema; 450-570AU - High erythema; over 570AU - Extreme erythema |
| Measure | Description | Time Frame |
|---|---|---|
| Superficial Plexus Depth | The difference in the change in superficial plexus depth (μm) measured by angiographic OCT. | Day 1, Day 15, Day 29 and Day 57 |
| Blood Vessel Diameter | The difference in the mean blood vessel diameter (μm) measured by angiographic OCT. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael J Cork, MB.ChB | The University of Sheffield & Sheffield Teaching Hospitals NHS FT | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sheffield Dermatology Research, University of Sheffield Medical School, The Royal Hallamshire Hospital | Sheffield | South Yorkshire | S10 2JF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20004783 | 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. | |
| 19874334 | 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. |
| Label | URL |
|---|---|
| Atopic eczema in children - Guideline consultation: National Institute for Clinical Excellence, Department of Health, UK | View source |
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Some participants, who were currently using treatments for eczema, needed to undergo a 'wash out' period, where the use of these treatments was stopped, prior to the first study visit. The duration of the wash-out depended on the type of treatment, and varied from 7 days for emollients to 12 weeks for intravenous biologic therapies.
Recruitment started 20/11/2020 and ended 27/07/2021. 37 participants were recruited.
Recruitment was conducted by the Sheffield Dermatology Research Group in several ways:
General advertisement using posters. Email lists. Outpatient contact including local GP practices.
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| ID | Title | Description |
|---|---|---|
| FG000 | Betamethasone Valerate (0.1%) Cream LEFT/Crisaborole (2%) Ointment RIGHT | All participants who treated the left forearm with Betamethasone valerate (0.1%) cream and the right forearm with Crisaborole (2%) ointment. Twice daily application for 4 weeks (randomised site allocation). |
| FG001 | Crisaborole (2%) Ointment LEFT/Betamethasone Valerate (0.1%) Cream RIGHT | All participants who treated the left forearm with Crisaborole (2%) ointment and the right forearm with Betamethasone valerate (0.1%) cream. Twice daily for 4 weeks (randomised site allocation). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Enrolled | All enrolled participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Epidermal Thickness | The difference in the change in epidermal thickness, measured by structural OCT, between the sites treated with crisaborole (2%) ointment and betamethasone valerate (0.1%) cream. | Posted | Mean | 95% Confidence Interval | µm | Day 1 - Day 57 |
|
Incidences of adverse events were collected from the date of the first participant's enrolment (10/12/2020) until the date the last participant completed (24/09/2021). Adverse event data was collected over a period of 9 months.
The definition of AE for SMART is:
"Any untoward medical occurrence in a participant to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product."
The definition of SAE is expanded to include a point that any complications that occur during hospitalisation are to be documented as AEs. If a complication prolongs hospitalisation, this is an SAE. Elective treatment is not an AE.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Betamethasone Valerate (0.1%) Cream | Adverse events that can be attributed to betamethasone valerate (0.1% cream |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment | Abdominal and gastrointestinal infections |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site papules | General disorders | MedDRA (Unspecified) | Systematic Assessment | General disorders and administration site conditions |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Simon Danby | University of Sheffield | 0114 2268515 | s.danby@sheffield.ac.uk |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 27, 2021 | Jun 21, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 16, 2021 | Jun 21, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 28, 2021 | Jun 21, 2023 | ICF_002.pdf |
Not provided
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| D003872 | Dermatitis |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C543085 | crisaborole |
| D009824 | Ointments |
| D001624 | Betamethasone Valerate |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D001623 | Betamethasone |
| D011246 | Pregnadienetriols |
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An observer-blind forearm-controlled clinical trial in 37 AD patients, wherein each participant will undergo 4 weeks treatment with crisaborole (2%) ointment on one forearm and betamethasone valerate (0.1%) cream on the other (twice daily application in each case and randomised site allocation). At the start of the study the skin of the test sites (forearms) will be clear of the signs of AD so that the investigation focuses on local adverse effects on the skin as opposed to anti-inflammatory effects (focus on local adverse effects and not clinical efficacy). The condition of the skin will be assessed before, during and after treatment.
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Allocation of the treatments to the test sites (right/left forearm) will be randomised (to avoid site position-dependent artefacts) Observer-blind - The collection of study data will be conducted in a separate area (dedicated skin barrier research suite) by a separate team (comprising skilled dermatology researchers) who will be blind.
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| betamethasone valerate 0.1% cream | Drug | twice daily application on one forearm for 4 weeks (randomised site allocation) |
|
|
| Day 1, Day 15, Day 29 and Day 57 |
| TEWL - Skin Barrier Function | Analysis of the change in Trans-Epidermal Water Loss (TEWL, relates to skin barrier function) during and after treatment. TEWL measurements on day 1, day 15, day 29 and day 57. | Day 1, Day 15, Day 29 and Day 57 |
| TEWL - After Tape-stripping | The difference in skin barrier integrity (TEWLts20) after 28 days treatment. TEWL measurements after tape-stripping (TEWLts20) on day 29 | on Day 29, after 28 days treatment |
| Comparison of TEWL - After Tape-stripping | The difference in skin barrier integrity (TEWLts20) after 28 days treatment. TEWL measurements after tape-stripping (TEWLts20) on day 29 | on Day 29, after 28 days treatment |
| Skin Dryness | The difference in the change in visual skin dryness during and after treatment. Visual skin dryness scored on day 1, day 15, day 29 and day 57. Visual skin dryness was scored using the following: 0 - Absent; 1 - Faint scaling, faint roughness and dull appearance; 2 - Small scales in combination with a few larger scales, slight roughness, whitish appearance; 3 - Small and larger scales uniformly distributed, definite roughness, possibly slight redness and possibly a few superficial cracks; 4 - Dominated by large scales, advanced roughness, redness present, eczematous changes and cracks. The lower the visual dryness score, the better the condition of the skin. | Visual skin dryness scored on day 1, day 15, day 29 and day 57 |
| Natural Moisturising Factor (NMF) | The difference in Natural Moisturising Factor (NMF, filaggrin breakdown products) levels at the end of treatment. 3 NMF components were measured: Urocanic acid (UCA), Pyrrolidone carboxylic acid (PCA) and Free amino acids (FAA) and are expressed together as total NMF (tNMF). | Day 29 |
| Comparison of Natural Moisturising Factor (NMF) Between Treatments | The difference in Natural Moisturising Factor (NMF, filaggrin breakdown products) levels at the end of treatment. 3 NMF components were measured: Urocanic acid (UCA), Pyrrolidone carboxylic acid (PCA) and Free amino acids (FAA) and are expressed together as total NMF (tNMF). | Day 29 |
| Change in Visual Redness/Erythema During and After 28 Days Treatment | The difference in the change in visual skin redness during and after treatment. Visual skin redness scored on day 1, day 15, day 29 and day 57 by an experienced grader. Visual skin redness was scored using the following: 0 - No redness; 0.5/+ - Slight patchy erythema, barely perceptible; 1 - Slight uniform erythema, mild erythema; 2 - Moderate uniform erythema, moderate erythema; 3 - Strong erythema, marked erythema. The higher the visual redness score, the more inflamed the skin looks to the naked eye. | Visual skin redness scored on day 1, day 15, day 29 and day 57 |
| Day 1, Day 15, Day 29 and Day 57. |
| Blood Vessel Density | The difference in the change in blood vessel density (segments/mm²) measured by angiographic OCT. Angiographic OCT images taken on Day 1, Day 15, Day 29 and Day 57. | Day 1, Day 15, Day 29 and Day 57. |
| Collagen Matrix Index | The difference in the change in collagen matrix index measured by polarisation sensitive (PS-)OCT. This metric relates to the arrangement and density of collagen fibres within the skin and is informed by birefringence data. Inhibition of collagen synthesis is an adverse effect associated with epidermal atrophy that occurs following long-term use of topical corticosteroids. There is no range for this measurement. The higher the level of change, the more damage has been done to the epidermis. | Day 1 and Day 29. |
| Carboxylate 1 Levels | The difference in the change in carboxylate 1 levels (indirect measure of NMF levels, not to be confused with direct quantification from stratum corneum samples by HPLC) in the stratum corneum measured by FTIR spectroscopy. FTIR spectra of the skin surface taken on Day 1, Day 15, Day 29 and Day 57. Carboxylate 1 is a component of Natural Moisturising Factors and relates to how well the skin retains water. There is no range for this measurement. The greater the value, the less able the skin is to hold onto water. | Day 1, Day 15, Day 29 and Day 57. |
| Carboxylate 2 Levels | The difference in the change in carboxylate 2 levels (indirect measure of NMF levels, not to be confused with direct quantification from stratum corneum samples by HPLC) in the stratum corneum measured by FTIR spectroscopy. FTIR spectra of the skin surface taken on Day 1, Day 15, Day 29 and Day 57. Carboxylate 2 is a component of Natural Moisturising Factors and relates to how well the skin retains water. There is no range for this measurement. The greater the value, the less able the skin is to hold onto water. | Day 1, Day 15, Day 29 and Day 57. |
| Stratum Corneum Lipid Structure | The difference in stratum corneum lipid structure measured by FTIR spectroscopy in conjunction with tape-stripping. FTIR spectra taken through the stratum corneum during tape-stripping on Day 29. Lipid chain structure was assessed by quantifying the mean frequency of the lipid peak at 2850 cm-1 (corresponding to the CH2 group of lipids). There is no range for this measurement. The higher the absorbance, the less ordered the lipid packing and weaker the structural integrity of the skin. | Day 29 |
| FLG Mutation Carriers | Number of FLG loss-of-function mutation carriers | Saliva samples at Day 1 |
| Descriptive Tabulations of TEWL by Mutation Status | Descriptive tabulations of TEWL by mutation status. | Day 1, Day 15, Day 29 and Day 57 |
| Epidermal Thickness by Mutation Status | Descriptive tabulations of epidermal thickness (structural OCT derived) by mutation status. | Day 1, Day 15, Day 29 and Day 57. |
| 19494826 | 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. |
| 19817751 | 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. |
| 15080802 | 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. |
| 18079551 | 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. |
| 16384751 | 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. |
| 20819086 | 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. |
| 22963149 | 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. |
| 29675335 | 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. |
| 18621555 | 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. |
| 27251427 | 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. |
| 18298945 | 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. |
| 19727117 | 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. |
| 25594610 | 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. |
| 24328907 | 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. |
| 21261659 | 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. |
| 24688811 | 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. |
| 26994359 | 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. |
| 22995032 | 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. |
| 11231311 | 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. |
| 16420534 | 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. |
| 26551528 | 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. |
| 12603860 | 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. |
| Danby SG, Wan H, Chittock J et al. Characterisation of the skin barrier defect in atopic dermatitis using in vivo ATR-FTIR molecular spectroscopy. J Invest Dermatol 2016; 136: S182. | View source |
| Lu Z, et al. Optical coherence tomography demonstrates differential epidermal thinning of human forearm volar skin after 2 weeks application of a topical corticosteroid vs a non-steroidal anti-inflammatory alternative. Proc. SPIE 2013; 85 | View source |
| Takada S, Naito S, Sonoda J et al. Noninvasive In Vivo Measurement of Natural Moisturizing Factor Content in Stratum Corneum of Human Skin by Attenuated Total Reflection Infrared Spectroscopy. Applied Spectroscopy 2012; 66: 26-32. | View source |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Atopic dermatitis as defined by UK working party diagnostic criteria | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | Analysis of Change in Objective Erythema | Analysis of the difference in the change in skin redness/erythema (relating to tolerability) during and after 28 days treatment determined by Mexameter measured on day 1, day 15, day 29 and day 57. The Mexameter device has a range of 0-999AU (arbitrary units) and the lower the value, the better the condition of the skin. Objective redness can be classified using the following scale: 0-170AU - No erythema; 170-330AU - Minimal erythema; 330-450AU - Diffuse erythema; 450-570AU - High erythema; over 570AU - Extreme erythema | 35 participants had complete data at Day 1. Each participant was expected to complete 56 days of treatment. A total of 5 participants were withdrawn before this point and so only 32 participants had data available for analysis at Day 29 and 57. | Posted | Mean | 95% Confidence Interval | AU | Day 1, Day 15, Day 29 and Day 57 |
|
|
|
| Secondary | TEWL - Skin Barrier Function | Analysis of the change in Trans-Epidermal Water Loss (TEWL, relates to skin barrier function) during and after treatment. TEWL measurements on day 1, day 15, day 29 and day 57. | 35 participants had complete data at Day 1. Each participant was expected to complete 56 days of treatment. A total of 5 participants were withdrawn before this point and so only 32 participants had data available for analysis at Day 29 and 57. | Posted | Mean | 95% Confidence Interval | g/m²/h | Day 1, Day 15, Day 29 and Day 57 |
|
|
|
| Secondary | TEWL - After Tape-stripping | The difference in skin barrier integrity (TEWLts20) after 28 days treatment. TEWL measurements after tape-stripping (TEWLts20) on day 29 | Full Analysis Set | Posted | Mean | Standard Deviation | g/m²/h | on Day 29, after 28 days treatment |
|
|
|
| Secondary | Comparison of TEWL - After Tape-stripping | The difference in skin barrier integrity (TEWLts20) after 28 days treatment. TEWL measurements after tape-stripping (TEWLts20) on day 29 | Full Analysis Set | Posted | Mean | 95% Confidence Interval | g/m²/h | on Day 29, after 28 days treatment |
|
|
|
| Secondary | Skin Dryness | The difference in the change in visual skin dryness during and after treatment. Visual skin dryness scored on day 1, day 15, day 29 and day 57. Visual skin dryness was scored using the following: 0 - Absent; 1 - Faint scaling, faint roughness and dull appearance; 2 - Small scales in combination with a few larger scales, slight roughness, whitish appearance; 3 - Small and larger scales uniformly distributed, definite roughness, possibly slight redness and possibly a few superficial cracks; 4 - Dominated by large scales, advanced roughness, redness present, eczematous changes and cracks. The lower the visual dryness score, the better the condition of the skin. | Frequency of visual dryness scores on Day 1, Day 15, Day 29 and Day 57. | Posted | Count of Participants | Participants | Visual skin dryness scored on day 1, day 15, day 29 and day 57 |
|
|
|
| Secondary | Natural Moisturising Factor (NMF) | The difference in Natural Moisturising Factor (NMF, filaggrin breakdown products) levels at the end of treatment. 3 NMF components were measured: Urocanic acid (UCA), Pyrrolidone carboxylic acid (PCA) and Free amino acids (FAA) and are expressed together as total NMF (tNMF). | Full Analysis Set | Posted | Mean | Standard Deviation | moles/µg protein | Day 29 |
|
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| Secondary | Comparison of Natural Moisturising Factor (NMF) Between Treatments | The difference in Natural Moisturising Factor (NMF, filaggrin breakdown products) levels at the end of treatment. 3 NMF components were measured: Urocanic acid (UCA), Pyrrolidone carboxylic acid (PCA) and Free amino acids (FAA) and are expressed together as total NMF (tNMF). | Full Analysis Set | Posted | Mean | 95% Confidence Interval | nmoles/µg protein | Day 29 |
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| Secondary | Change in Visual Redness/Erythema During and After 28 Days Treatment | The difference in the change in visual skin redness during and after treatment. Visual skin redness scored on day 1, day 15, day 29 and day 57 by an experienced grader. Visual skin redness was scored using the following: 0 - No redness; 0.5/+ - Slight patchy erythema, barely perceptible; 1 - Slight uniform erythema, mild erythema; 2 - Moderate uniform erythema, moderate erythema; 3 - Strong erythema, marked erythema. The higher the visual redness score, the more inflamed the skin looks to the naked eye. | Frequency of visual dryness scores on Day 1, Day 15, Day 29 and Day 57. | Posted | Count of Participants | Participants | Visual skin redness scored on day 1, day 15, day 29 and day 57 |
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| Other Pre-specified | Superficial Plexus Depth | The difference in the change in superficial plexus depth (μm) measured by angiographic OCT. | Full Analysis Set | Posted | Mean | Standard Deviation | µm | Day 1, Day 15, Day 29 and Day 57 |
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| Other Pre-specified | Blood Vessel Diameter | The difference in the mean blood vessel diameter (μm) measured by angiographic OCT. | Full Analysis Set | Posted | Mean | Standard Deviation | µm | Day 1, Day 15, Day 29 and Day 57. |
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| Other Pre-specified | Blood Vessel Density | The difference in the change in blood vessel density (segments/mm²) measured by angiographic OCT. Angiographic OCT images taken on Day 1, Day 15, Day 29 and Day 57. | Full Analysis Set | Posted | Mean | Standard Deviation | segments/mm² | Day 1, Day 15, Day 29 and Day 57. |
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| Other Pre-specified | Collagen Matrix Index | The difference in the change in collagen matrix index measured by polarisation sensitive (PS-)OCT. This metric relates to the arrangement and density of collagen fibres within the skin and is informed by birefringence data. Inhibition of collagen synthesis is an adverse effect associated with epidermal atrophy that occurs following long-term use of topical corticosteroids. There is no range for this measurement. The higher the level of change, the more damage has been done to the epidermis. | Full Analysis Set | Posted | Mean | Standard Deviation | AU | Day 1 and Day 29. |
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| Other Pre-specified | Carboxylate 1 Levels | The difference in the change in carboxylate 1 levels (indirect measure of NMF levels, not to be confused with direct quantification from stratum corneum samples by HPLC) in the stratum corneum measured by FTIR spectroscopy. FTIR spectra of the skin surface taken on Day 1, Day 15, Day 29 and Day 57. Carboxylate 1 is a component of Natural Moisturising Factors and relates to how well the skin retains water. There is no range for this measurement. The greater the value, the less able the skin is to hold onto water. | Full Analysis Set | Posted | Mean | Standard Deviation | absorbance units | Day 1, Day 15, Day 29 and Day 57. |
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| Other Pre-specified | Carboxylate 2 Levels | The difference in the change in carboxylate 2 levels (indirect measure of NMF levels, not to be confused with direct quantification from stratum corneum samples by HPLC) in the stratum corneum measured by FTIR spectroscopy. FTIR spectra of the skin surface taken on Day 1, Day 15, Day 29 and Day 57. Carboxylate 2 is a component of Natural Moisturising Factors and relates to how well the skin retains water. There is no range for this measurement. The greater the value, the less able the skin is to hold onto water. | Full Analysis Set | Posted | Mean | Standard Deviation | absorbance units | Day 1, Day 15, Day 29 and Day 57. |
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| Other Pre-specified | Stratum Corneum Lipid Structure | The difference in stratum corneum lipid structure measured by FTIR spectroscopy in conjunction with tape-stripping. FTIR spectra taken through the stratum corneum during tape-stripping on Day 29. Lipid chain structure was assessed by quantifying the mean frequency of the lipid peak at 2850 cm-1 (corresponding to the CH2 group of lipids). There is no range for this measurement. The higher the absorbance, the less ordered the lipid packing and weaker the structural integrity of the skin. | Full Analysis Set | Posted | Mean | Standard Deviation | absorbance units | Day 29 |
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| Other Pre-specified | FLG Mutation Carriers | Number of FLG loss-of-function mutation carriers | Full Analysis Set | Posted | Count of Participants | Participants | Saliva samples at Day 1 |
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| Other Pre-specified | Descriptive Tabulations of TEWL by Mutation Status | Descriptive tabulations of TEWL by mutation status. | Full Analysis Set | Posted | Mean | Standard Deviation | g/m²/h | Day 1, Day 15, Day 29 and Day 57 |
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| Other Pre-specified | Epidermal Thickness by Mutation Status | Descriptive tabulations of epidermal thickness (structural OCT derived) by mutation status. | Full Analysis Set | Posted | Mean | Standard Deviation | µm | Day 1, Day 15, Day 29 and Day 57. |
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| 0 |
| 37 |
| 0 |
| 37 |
| 7 |
| 37 |
| EG001 | Crisaborole (2%) Ointment | Adverse events that can be attributed to crisaborole (2%) ointment | 0 | 37 | 0 | 37 | 7 | 37 |
| EG002 | Systemic Adverse Events | Adverse events that cannot be attributed to either intervention | 0 | 37 | 1 | 37 | 32 | 37 |
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| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Candida infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment | Thrush |
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| Nasopharyngitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment | Sneezing and itchy eyes |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Application site reaction | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Lower respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Upper abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment | Stomach pain |
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| COVID-19 infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment | Hyperpigmentation |
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| Chills | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Application site pruritis | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment | Muscle/back pain |
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| Application site bruise | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Nerve compression | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment | Trapped nerve |
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| Infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment | Infected nail bed |
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| Dizziness | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Hernia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Skin abrasion | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Application site rash | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Pain | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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Not provided
Not provided
Not provided
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D011245 |
| Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| Baseline to Day 15 |
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| Day 29 to Day 57 |
|
|
| Baseline to Day 15 |
|
|
| Day 29 to Day 57 |
|
|
| 1 |
|
| 2 |
|
| Day 15 |
|
|
| Day 29 |
|
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| Day 57 |
|
|
| Urocanic Acid (UCA) |
|
| Free Amino Acids (FAA) |
|
| Urocanic Acid (UCA) |
|
| Free Amino Acids (FAA) |
|
| 0.5 |
|
| 1 |
|
| Day 15 |
|
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| Day 29 |
|
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| Day 57 |
|
|
| Day 1 to Day 15 |
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| Day 29 to Day 57 |
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| Day 1 to Day 15 |
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| Day 29 to Day 57 |
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| Day 1 to Day 15 |
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| Day 29 to Day 57 |
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| Day 1 to Day 15 |
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| Day 29 to Day 57 |
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| Day 1 to Day 15 |
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| Day 29 to Day 57 |
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| Day 15 |
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| Day 29 |
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| Day 57 |
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| Day 15 |
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| Day 29 |
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| Day 57 |
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