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

NCT02347501 | Completed Phase 2 DMC

• 2 other identifiers: DPIP-2012-022012-005483-10
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (1)

• The change in PASI during treatment with sitagliptin for participants with psoriasis undergoing NB-UVB light therapy compared to psoriasis patients undergoing NB-UVB light therapy who are allocated randomly to not receive any additional treatment.

  24 weeks

Secondary Outcomes (19)

• The incidence of adverse events in the patients treated with sitagliptin and in the patients receiving no additional treatment

  24 and 36 weeks

• The change in DLQI in patients receiving treatment with sitagliptin compared to the change in DLQI in patients receiving no additional treatment.

  24 and 36 weeks

• The change in PASI over 36 weeks in patients treated with sitagliptin compared to patients receiving no additional treatment.

  36 weeks

• The change in blood pressure in patients treated with sitagliptin compared to patients receiving no additional treatment.

  24 and 36 weeks

• The change in serum cytokines in patients treated with sitagliptin compared to patients receiving no additional treatment.

  24 and 36 weeks

Other Outcomes (11)

• The changes in skin levels of cells in patients treated with sitagliptin and in patients receiving no additional treatment in a sub-group of patients willing to undergo skin biopsies.

  24 weeks

• The genetic, and/or epigenetic, profile that predicts best response to NB-UVB light therapy and to sitagliptin therapy.

  Baseline

• The changes in expression of cells in skin in patients treated with sitagliptin and in patients receiving no additional treatment in a sub-group of patients willing to undergo skin biopsies.

  24 weeks

Study Arms (2)

A

EXPERIMENTAL

Sitagliptin 100mg once daily orally or 50mg once daily for participants with moderate kidney disease for 24 weeks and narrowband ultraviolet-B (NBUVB) phototherapy. NBUVB light therapy is continued until the participants' psoriasis clears (\<1% body surface area involved).

Drug: Sitagliptin (Januvia)

B

NO INTERVENTION

No additional treatment other than narrowband ultraviolet-B (NBUVB) phototherapy. NBUVB light therapy is continued until the participants' psoriasis clears (\<1% body surface area involved).

Interventions

Sitagliptin (Januvia) DRUG

Sitagliptin 100mg tablet once daily (or 50mg once daily for participants with moderate kidney disease) for twenty four weeks in patients due to undergo NBUVB light therapy.

Also known as: Januvia

A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a diagnosis of generalized chronic plaque and/or guttate psoriasis;
• Are male and female patients aged between 18 and 75 years inclusive;
• Have a psoriasis area and severity index (PASI) greater than 7 despite use of topical therapies;
• Are due to undergo NB-UVB light therapy;
• Have not required systemic psoriasis therapy during the past eight weeks;
• Are unlikely to require systemic therapy for the duration of clinical trial involvement;
• Have a negative pregnancy test at screening (women of child bearing potential only); and
• Are willing to sign voluntarily a statement of informed consent to participate in the study.

You may not qualify if:

• People with any of the following conditions will be excluded from the study:
• Photosensitive disorders (lupus erythematosis etc);
• Diabetes mellitus;
• Use of medications that can cause photosensitivity;
• Use of GLP-1 analogue therapy;
• Conditions that could be made worse by phototherapy (cataract, epilepsy, etc);
• Allergy or hypersensitivity to Januvia®;
• Severe kidney disease as defined by a previous diagnosis of chronic kidney disease in the presence of an estimated glomerular filtration rate (eGFR) of less than 30ml/min/1.73m2;
• Recent (within 8 weeks) receipt of NB-UVB light;
• Current or recent (within 8 weeks) use of systemic therapy for psoriasis;
• Severe heart disease as defined by a previous diagnosis of heart disease and a left ventricular ejection fraction which is known to be less than 35% (as measured by echocardiogram or cardiac catheterisation study);
• Severe lung disease as defined by a previous diagnosis of chronic lung disease and a forced expiratory volume in 1 second (FEV1) or a forced vital capacity (FVC) that is known to be less than 50% that which would be estimated for a person of that age and gender;
• Severe liver disease as defined by a previous diagnosis of chronic liver disease in the presence of an alanine transferase concentration greater than 150 international units/L (greater than three times the upper limit of the normal reference range);
• Any other contraindications to Januvia® as stated in its SPC;
• Female patients of child bearing potential who are pregnant, breastfeeding, or unwilling to practice an acceptable barrier and/or hormonal method of contraception during participation in the study - abstinence will be permitted only if it is in keeping with a person's lifestyle;

Sponsors & Collaborators

• University College Dublin: lead

Study Sites (1)

UCD Clinical Research Centre, St Vincent's University Hospital

Dublin, Ireland

Location

Related Publications (30)

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  PMID: 15872205 RESULT

• 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.

  PMID: 19641206 RESULT

• 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.

  PMID: 8763423 RESULT

• 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.

  PMID: 18384439 RESULT

• 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.

  PMID: 16778789 RESULT

• 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.

  PMID: 21404914 RESULT

• 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.

  PMID: 22056790 RESULT

• 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.

  PMID: 12917302 RESULT

• 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.

  PMID: 20071701 RESULT

• 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.

  PMID: 12813013 RESULT

• 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.

  PMID: 21206136 RESULT

• 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.

  PMID: 20015525 RESULT

• 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.

  PMID: 20412573 RESULT

• Lamanna C, Monami M, Bartoli N, Zannoni S, Mannucci E. Dipeptidyl peptidase- 4 inhibitors and cardiovascular events: a protective effect? Diabetologia. 2011;54:S109.

  RESULT

• 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.

  PMID: 15009298 RESULT

• 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.

  PMID: 21244768 RESULT

• 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.

  PMID: 21623773 RESULT

• 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.

  PMID: 19380660 RESULT

• 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.

  PMID: 20103558 RESULT

• 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.

  PMID: 20655127 RESULT

• 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.

  PMID: 21744074 RESULT

• 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.

  RESULT

• 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.

  PMID: 22691169 RESULT

• 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.

  PMID: 22025784 RESULT

• 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.

  PMID: 15327535 RESULT

• 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.

  PMID: 19811850 RESULT

• 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.

  PMID: 12622624 RESULT

• 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.

  PMID: 20716226 RESULT

• 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.

  PMID: 19466961 RESULT

• 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.

  PMID: 26767505 DERIVED

Related Links

• A web-based randomization plan generator.

MeSH Terms

Conditions

Psoriasis

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Brian Kirby, MD FRCPI

  University College Dublin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: January 27, 2015
• Study Start: November 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

IE (1)