Dipeptidyl Peptidase-4 Inhibition and Narrow-band Ultraviolet-B Light in Psoriasis (DINUP)

Summary

The primary purpose of this study is to determine if sitagliptin (Januvia®) improves psoriasis severity after 24 weeks of treatment in 60 participants with psoriasis who do not have type 2 diabetes mellitus, and who are due to receive a course of narrowband ultraviolet-B phototherapy (NB-UVB). The investigators will compare the change in psoriasis severity in 60 participants treated with both sitagliptin and NB-UVB to 60 participants treated with NB-UVB alone. Participants will be recruited from two centres and after a 3 week run-in period will be followed prospectively for 36 weeks. Participants will be stratified by centre, plasma glycated haemoglobin level (HbA1c), obesity status and previous response to NB-UVB, after which they will be randomly allocated to Arm A or Arm B. Participants will be treated with either sitagliptin for 24 weeks and NB-UVB (Arm A), or NB-UVB alone (Arm B). Both the research participants and the investigators will be aware of the trial arm to which the research participant has been allocated randomly (open-label study). Research participants are prohibited from using systemic psoriasis therapy for the duration of their trial involvement. Participants will be assessed at 8 study visits over 39 weeks. Participants will complete questionnaires, have a medical history recorded and physical examination, blood sampling and skin biopsies taken (in a small number of willing participants at 2 visits). The following endpoints will be analysed: Changes in psoriasis severity at 24 and 36 weeks; changes in validated quality of life scores; incidence of adverse events; incidence of discontinuation of one of the study IMPs, time to relapse of psoriasis; changes in cardiovascular disease risk factor profiles; changes in cytokines, hormones, expression of immune proteins in blood and skin biopsies; and genetic profiles that predicts best response to sitagliptin therapy. The investigators hypothesize that sitagliptin therapy decreases psoriasis severity.

Timeline

Start

2013-11

Primary completion

2016-12

Completion

2016-12

Publications

• Results Schon MP, Boehncke WH. Psoriasis. N Engl J Med. 2005 May 5;352(18):1899-912. doi: 10.1056/NEJMra041320. No abstract available.
• Results Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009 Jul 30;361(5):496-509. doi: 10.1056/NEJMra0804595. No abstract available.
• Results Novelli M, Savoia P, Fierro MT, Verrone A, Quaglino P, Bernengo MG. Keratinocytes express dipeptidyl-peptidase IV (CD26) in benign and malignant skin diseases. Br J Dermatol. 1996 Jun;134(6):1052-6.
• Results van Lingen RG, van de Kerkhof PC, Seyger MM, de Jong EM, van Rens DW, Poll MK, Zeeuwen PL, van Erp PE. CD26/dipeptidyl-peptidase IV in psoriatic skin: upregulation and topographical changes. Br J Dermatol. 2008 Jun;158(6):1264-72. doi: 10.1111/j.1365-2133.2008.08515.x. Epub 2008 Mar 29.
• Results Thielitz A, Reinhold D, Vetter R, Bank U, Helmuth M, Hartig R, Wrenger S, Wiswedel I, Lendeckel U, Kahne T, Neubert K, Faust J, Zouboulis CC, Ansorge S, Gollnick H. Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation. J Invest Dermatol. 2007 May;127(5):1042-51. doi: 10.1038/sj.jid.5700439. Epub 2006 Jun 15.
• Results Ohnuma K, Hosono O, Dang NH, Morimoto C. Dipeptidyl peptidase in autoimmune pathophysiology. Adv Clin Chem. 2011;53:51-84. doi: 10.1016/b978-0-12-385855-9.00003-5.
• Results Nishioka T, Shinohara M, Tanimoto N, Kumagai C, Hashimoto K. Sitagliptin, a dipeptidyl peptidase-IV inhibitor, improves psoriasis. Dermatology. 2012;224(1):20-1. doi: 10.1159/000333358. Epub 2011 Nov 1.
• Results Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, Bossuyt PM, Bos JD, de Rie MA. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003 Aug 14;349(7):658-65. doi: 10.1056/NEJMoa021359.
• Results Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, Guzzo C, Xia Y, Zhou B, Li S, Dooley LT, Goldstein NH, Menter A; ACCEPT Study Group. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010 Jan 14;362(2):118-28. doi: 10.1056/NEJMoa0810652.
• Results Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003 Jun;111(12):1805-12. doi: 10.1172/JCI18921. No abstract available.
• Results Hattori S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr J. 2011;58(1):69-73. doi: 10.1507/endocrj.k10e-382. Epub 2010 Dec 28.
• Results Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D'Angelo A, Cicero AF. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients. Metabolism. 2010 Jun;59(6):887-95. doi: 10.1016/j.metabol.2009.10.007. Epub 2009 Dec 16.
• Results Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010 Apr 22;10:7. doi: 10.1186/1472-6823-10-7.
• Results Lamanna C, Monami M, Bartoli N, Zannoni S, Mannucci E. Dipeptidyl peptidase- 4 inhibitors and cardiovascular events: a protective effect? Diabetologia. 2011;54:S109.
• Results Chodorowska G, Wojnowska D, Juszkiewicz-Borowiec M. C-reactive protein and alpha2-macroglobulin plasma activity in medium-severe and severe psoriasis. J Eur Acad Dermatol Venereol. 2004 Mar;18(2):180-3. doi: 10.1111/j.1468-3083.2004.00863.x.
• Results Gisondi P, Malerba M, Malara G, Puglisi Guerra A, Sala R, Radaeli A, Calzavara-Pinton P, Girolomoni G. C-reactive protein and markers for thrombophilia in patients with chronic plaque psoriasis. Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1195-202. doi: 10.1177/039463201002300423.
• Results Nisa N, Ahmed Q. High-sensitivity C-reactive protein in psoriasis. Int J Dermatol. 2012 Nov;51(11):1393-4. doi: 10.1111/j.1365-4632.2010.04761.x. Epub 2011 May 30. No abstract available.
• Results Mittal R, Malhotra S, Pandhi P, Kaur I, Dogra S. Efficacy and safety of combination Acitretin and Pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial. Arch Dermatol. 2009 Apr;145(4):387-93. doi: 10.1001/archdermatol.2009.5.
• Results Drucker DJ, Sherman SI, Gorelick FS, Bergenstal RM, Sherwin RS, Buse JB. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care. 2010 Feb;33(2):428-33. doi: 10.2337/dc09-1499. No abstract available.
• Results Hossler EW, Maroon MS, Mowad CM. Gastric bypass surgery improves psoriasis. J Am Acad Dermatol. 2011 Jul;65(1):198-200. doi: 10.1016/j.jaad.2010.01.001. Epub 2010 Jul 22.
• Results Hogan AE, Tobin AM, Ahern T, Corrigan MA, Gaoatswe G, Jackson R, O'Reilly V, Lynch L, Doherty DG, Moynagh PN, Kirby B, O'Connell J, O'Shea D. Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. Diabetologia. 2011 Nov;54(11):2745-54. doi: 10.1007/s00125-011-2232-3. Epub 2011 Jul 9.
• Results Ahern T, Tobin AM, Corrigan MA, Hogan AE, Kirby B, O'Shea D. Liraglutide Decreases Psoriasis Severity. Irish Journal of Medical Science. 2011;180(Supplement 13):S506.
• Results Ahern T, Tobin AM, Corrigan M, Hogan A, Sweeney C, Kirby B, O'Shea D. Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study. J Eur Acad Dermatol Venereol. 2013 Nov;27(11):1440-3. doi: 10.1111/j.1468-3083.2012.04609.x. Epub 2012 Jun 13.
• Results Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 2011 Nov;34(11):2474-6. doi: 10.2337/dc11-1099.
• Results Ibbotson SH, Bilsland D, Cox NH, Dawe RS, Diffey B, Edwards C, Farr PM, Ferguson J, Hart G, Hawk J, Lloyd J, Martin C, Moseley H, McKenna K, Rhodes LE, Taylor DK; British Association of Dermatologists. An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report. Br J Dermatol. 2004 Aug;151(2):283-97. doi: 10.1111/j.1365-2133.2004.06128.x.
• Results Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JYM, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010 Jan;62(1):114-135. doi: 10.1016/j.jaad.2009.08.026. Epub 2009 Oct 7.
• Results Markham T, Rogers S, Collins P. Narrowband UV-B (TL-01) phototherapy vs oral 8-methoxypsoralen psoralen-UV-A for the treatment of chronic plaque psoriasis. Arch Dermatol. 2003 Mar;139(3):325-8. doi: 10.1001/archderm.139.3.325.
• Results Ryan C, Renfro L, Collins P, Kirby B, Rogers S. Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis. Br J Dermatol. 2010 Nov;163(5):1056-63. doi: 10.1111/j.1365-2133.2010.09985.x.
• Results Kleinpenning MM, Smits T, Boezeman J, van de Kerkhof PC, Evers AW, Gerritsen MJ. Narrowband ultraviolet B therapy in psoriasis: randomized double-blind comparison of high-dose and low-dose irradiation regimens. Br J Dermatol. 2009 Dec;161(6):1351-6. doi: 10.1111/j.1365-2133.2009.09212.x. Epub 2009 Apr 10.
• Lynch M, Ahern TB, Timoney I, Sweeney C, Kelly G, Hughes R, Tobin AM, O'Shea D, Kirby B. Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial. Trials. 2016 Jan 15;17:29. doi: 10.1186/s13063-016-1157-z.

Drugs

Indications