title: Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease.
  
  
  METHODS
  This is a single centre, 39-week, prospective, randomised, open label, clinical trial of oral sitagliptin (Januvia(®)) in psoriasis patients who are due to undergo a course of narrow-band ultraviolet-B (NB-UVB) phototherapy. We plan to enrol 120 participants and allocate participants on a random and 1:1 basis to receive sitagliptin 100 mg daily for 24 weeks combined with NB-UVB or NB-UVB monotherapy. Participants will be followed up for 12 weeks after sitagliptin therapy is discontinued. The primary endpoint is the change in Psoriasis Area and Severity Index (PASI) 24 weeks after treatment initiation. Secondary endpoints include cumulative NB-UVB dose, number of NB-UVB treatments required to clear psoriasis, proportions of participants who achieve PASI-50 (50 % reduction in PASI from baseline), PASI-75, PASI-90 and the proportion of participants who relapse in each group. We will also analyse changes in cardiovascular disease risk factors, serum cytokine and hormone levels and peripheral blood mononuclear expression of immune proteins at 24 and 36 weeks. A subgroup of participants will have skin biopsies taken and analysed for skin levels and expression of immune cells, receptors, hormones and immune proteins. The genetic or epigenetic profile that predicts best response to DPP-4 inhibitor therapy will be analysed. The safety endpoints include the rate and severity of adverse events.
  
  
  CONCLUSIONS
  This is the first randomised clinical trial assessing dipeptidyl peptidase-4 inhibition therapy in psoriasis. We hypothesise that sitagliptin therapy in combination with NB-UVB improves psoriasis severity compared to NB-UVB monotherapy.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. lynchmaeve@yahoo.ie.
authors.forename: Maeve
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Endocrinology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. tomasbahern@physicians.ie.
authors.forename: Tomás B
authors.initials: TB
authors.lastname: Ahern
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. irenetimoney@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: Timoney
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. chsweene@tcd.ie.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Sweeney
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. gkellywinter@gmail.com.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. rossiehughes@gmail.com.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Dermatology Department, Adelaide and Meath Hospital Incorporating the National Children's Hospital, Tallaght, Dublin 24, Ireland. tobin.annemarie@gmail.com.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Tobin
authors.affiliation: Endocrinology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. info@dosheaendo.ie.
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. b.kirby@st-vincents.ie.
authors.forename: Brian
authors.initials: B
authors.lastname: Kirby
mesh_terms: D002985:Clinical Protocols; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D006801:Humans; D011446:Prospective Studies; D011565:Psoriasis / Q000628:therapy*; D011786:Quality Control; D018401:Sample Size; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D014467:Ultraviolet Therapy / Q000379:methods*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000068900:Sitagliptin Phosphate