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

 Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's
 population. It is characterised by keratinocyte hyperproliferation, by aberrant keratinocyte
 differentiation and by cutaneous inflammation.

 Dipeptidyl peptidase-4 (DPP-4) is expressed on keratinocytes and its activity is upregulated
 in psoriasis. DPP-4 inhibition suppresses keratinocyte proliferation and restores partially
 keratinocyte differentiation. The main site of DPP-4 activity is cluster of differentiation
 antigen 26 (CD26). CD26 is a marker of T cell activation and is a key molecule in the
 pathogenesis of autoimmune diseases. One case of DPP-4 inhibitor therapy improving psoriasis
 severity has been reported.

 Agents used to treat psoriasis target commonly the underlying inflammation. C-reactive
 protein (CRP) is a sensitive, systemic marker of inflammation. In people with type 2 diabetes
 (T2DM) DPP-4 inhibitor therapy decreases CRP concentrations. Serum CRP concentrations
 correlate with psoriasis severity and interventions that decrease the CRP concentration may
 decrease also psoriasis severity. Medications that improve insulin resistance may decrease
 also systemic inflammation and improve psoriasis. We have shown previously, in psoriasis
 patients without T2DM (both lean and obese), that the fasting insulin concentration and the
 homeostatic model of insulin resistance (measures of insulin resistance) correlate strongly
 with the psoriasis area and severity index (PASI, a measure of psoriasis severity: r=0.48,
 p<0.001; r=0.49, p<0.001).

 DPP-4 inhibitors prevent also the degradation of insulin secretagogues, such as glucagon-like
 peptide-1 (GLP-1), thereby ameliorating hyperglycaemia without causing hypoglycaemia. Due to
 this effect DPP-4 inhibitors are effective for the treatment of T2DM. Other interventions
 which increase GLP-1 receptor activation, such as roux-en-Y gastric bypass surgery and GLP-1
 analogue therapy, can improve also psoriasis severity.

 We have reported previously a significant improvement in two patients with psoriasis and
 diabetes treated with the GLP-1 analogue liraglutide. In a subsequent open study of 7
 patients with both psoriasis and type 2 diabetes we found a significant reduction in
 psoriasis severity and a significant improvement in quality of life following treatment with
 liraglutide.

 Name and Description of the Investigational Medicinal Products(s):

 Januvia® 100 mg tablets, which are film-coated tablets for oral ingestion that contain 100mg
 of the dipeptidyl peptidase-4 inhibitor sitagliptin.

 For research participants with moderate kidney disease (CrCl < 50 ml/min or eGFR < 50
 ml/min/1.73m2), a dose of 50mg per day of sitagliptin will be used.

 Potential risks and benefits:

 More than 1% of people who take Januvia® tablets experience upper respiratory tract infection
 (no greater incidence than with placebo), hypoglycaemia (no greater incidence than with
 placebo), headache or limb pain.

 The potential benefits of DPP-4 inhibition include decreased risk of cardiovascular disease
 and decreased risk of bone fracture.

 The anticipated benefits of Januvia® therapy in psoriasis patients without type 2 diabetes
 thus justify the potential risks.

 Description of and justification for the route of administration, dosage, dosage regimen and
 treatment period:

 This will be a two centre, thirty-nine week, prospective, randomized, open-label clinical
 trial of oral Januvia® (sitagliptin) tablets in 120 people with psoriasis without diabetes
 who are due to undergo a course of NB-UVB phototherapy.

 After a three week run-in period, where research participants will not receive the
 investigational medicinal product, research participants will be allocated randomly, after
 stratification by centre, by HbA1c level (HbA1c < 38mmol/mol or ≥ 38mmol/mol), BMI level (BMI
 < 30 kg/m2 or ≥ 30 kg/m2) and previous response to NB-UVB (achieved remission within 25
 exposures during most recent course of NBUVB or not) either to Arm A or to Arm B. Those who
 have not been exposed previously to NBUVB will be placed in the "did not achieve remission
 within 25 exposures" group. Research participants allocated to Arm A will receive a twenty
 six week supply of Januvia® tablets (DPP-4 Inhibitor) and will be instructed to ingest orally
 one 100mg tablet once daily (or 50mg once daily for participants with moderate kidney
 disease) for twenty four weeks. Research participants allocated to Arm B will receive no
 treatment (aside from usual medications and phototherapy). 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 will be prohibited from making any changes to the dose of medications
 used to treat psoriasis. Any other medications that are considered necessary for the
 participant's welfare and will not interfere with the study medication may be given at the
 discretion of the Investigator.

 Januvia® is licensed to improve glycaemic control for people with type 2 diabetes (T2DM). The
 Summary of Product Characteristics (SPC) states that the dose of Januvia® is 100mg once daily
 (using tablets for oral ingestion). For research participants with moderate kidney disease
 (CrCl < 50 ml/min or eGFR < 50 ml/min/1.73m2), the Summary of Product Characteristics (SPC)
 states that the dose of Januvia® is 50mg once daily (using tablets for oral ingestion). In
 keeping with this all participants with an eGFR < 50ml/min/1.73m2 who are due to receive
 Januvia® will receive 50mg once daily.

 Study Hypothesis:

 Dipeptidyl peptidase-4 inhibitor therapy decreases psoriasis severity.

 Statement of Trial Conduct:

 This trial will be conducted in compliance with the protocol, with the guidelines of the
 Declaration of Helsinki (see Appendix 2), with the International Conference of Harmonisation
 Tripartite Guideline on Good Clinical Practice, with all applicable regulatory requirements
 and with data protection legislation (Data Protection Act 1988 and Data Protection Amendment
 Act 2003)

 Cohort:

 The population to be studied will be psoriasis patients with type 2 diabetes.

 We plan to enrol 120 research participants in total. Research participants will be recruited
 from two centres: St Vincent's University Hospital, Elm Park, Dublin 4 and Adelaide and Meath
 Hospital, Tallaght, Dublin 24. These hospitals provide outpatient dermatology services.
 Psoriasis patients attending these centres who have a psoriasis area and severity index
 (PASI) greater than 7 and who are due to undergo a course of NB-UVB phototherapy will be
 considered potentially eligible research participants and will be invited to attend for a
 screening visit.

 Identification and Recruitment:

 Potentially eligible research participants will be identified through use of patient
 databases in St Vincent's University Hospital and in Adelaide and Meath Hospital and through
 review of healthcare records in St Vincent's University Hospital and in Adelaide and Meath
 Hospital.

 Potentially eligible research participants will be recruited in one of two ways by the study
 investigators or suitably qualified designee. One of these two ways will be during a clinic
 visit by the study investigators or suitably qualified designee. The other of the two ways
 will be mailing a letter of invitation.

 A record of all medication taken by study participants in the month before visit 1 and
 concomitant medication a participant takes throughout the study will be recorded on the
 appropriate page of the Case Report Form (CRF).

 Treatment compliance of research participants will be measured by pill counts. Research
 participants will be instructed to bring opened, unopened and empty investigational medicinal
 product packages to each visit in order to allow the assessment of compliance with study
 treatment. A record of all investigational medicinal product dispensed and returned will be
 documented on the investigational medicinal product dispensing and accountability log. Blood
 taken during stages when the participant is expected to be taking drug therapy will be used
 for future determination of plasma glucose and glycated haemoglobin concentrations. These
 concentrations will also be used to help ascertain compliance with the allocated treatment
 regimen.

 Blood samples for measurement of laboratory parameters will be taken between the hours of
 0800 and 1200 after a greater than 12 hour overnight fast (with the exception of the
 Screening Visit when participants can attend in a non fasting state) and before ingestion of
 the study investigational medicinal product. The blood will be taken by a senior clinician,
 or suitably qualified designee, with competence and experience in the procedure of
 venepuncture.

 Thirty millilitres (30ml) of blood will be drawn during visit 1, and 73.5 ml during visit 2.
 Sixty millilitres (60ml) of blood will be drawn from the research participants during visits
 3 to 5, and at visit 7. During visits 6 and 8, 67.5 mls of blood will be drawn.Blood will be
 drawn into vacutainer tubes containing either ethylenediaminetetraacetic acid (EDTA), lithium
 heparin, sodium fluoride, clot activator or a DPP-4 inhibitor cocktail.

 Each research participant will be asked to give a blood sample for genetic analysis at the
 2nd Visit. These genetic samples will be analysed to try determine the genetic, and/or
 epigenetic, profile that predicts best response to DPP-4 inhibitor therapy.

 Whole blood will be stored for future DNA extraction using the protocols detailed in the
 Molecular Medicine Ireland Guideline for Standardised Biobanking (First Edition 2010). This
 involves drawing blood into a blood tube containing EDTA and storing the blood tube at -20°C
 in secure, dedicated freezers in the Research Laboratories in the Education and Research
 Centre in St Vincent's University Hospital. The blood will be stored within 12 hours of blood
 collection.

 Blood that has been stored for future DNA extraction will be destroyed once the DNA analyses
 are complete. Disposal of this material will be in accordance with current practice in this
 unit and with the written protocols in place in this unit. Disposal will involve the use of
 solid plastic waste containers which will be sent for incineration.

 To protect the research participant's identity, a unique identification code will be assigned
 by the Investigator, or authorised designee, to each participant's genetic sample and used in
 lieu of the participant's name. This coded form of identification, instead of the
 participant's name, will appear on all documents/databases.

 Statistical Analysis Plan:

 Demographic and baseline clinical data will be summarized using descriptive statistics by
 treatment group. Similarly, the primary and secondary efficacy variables will be summarized
 using descriptive statistics by treatment group.

 Data from research participants who are not allocated to either arm of the study and who do
 not receive a supply of the investigational medicinal product will be excluded from
 statistical analyses.

 T tests (or the appropriate alternative for non-parametric data), using two-sided tests, will
 be used to test for significant differences between the sets of data obtained. The
 independent samples T test will be used to assess for differences between the effects of the
 test product (Januvia®) compared to the effects of no additional treatment. Chi square
 analyses will be used to test for significant differences in categorical variables between
 the sets of data obtained.

 Subgroup analyses will be performed on those research participants who:

 complete the visit 6 assessment; have severe psoriasis; have non-severe psoriasis; are male;
 are female; are obese; and are older than 45 years.

 Packaging and Labelling:

 All study medication will be labelled and stored in accordance with Annex 13 of the EU
 guidelines of good manufacturing practice in respect of investigational medicinal products
 for human use, the SPC and hospital procedures.

 Screening visit (Visit 1, Week -3) Before any screening examinations take place potentially
 eligible research participants will be given a full explanation as to what participation in
 the study would involve - this will be done both verbally and in writing in the form of a
 written participant information leaflet. Potential research participants will be given
 sufficient time to consider their participation in the study and to ask any questions
 concerning the study. Potential research participants who are willing to take part in the
 study will be asked then to sign an informed consent form. No study related procedures will
 take place for any research participant before the informed consent form has been signed.

 The following assessments will then be performed:

 1. Checking against inclusion and exclusion criteria;

 2. Obtaining demographic information;

 3. Obtaining a detailed medical history (previously diagnosed illnesses etc);

 4. Obtaining a detailed medication history for the previous month;

 5. Measurement of weight, blood pressure and heart rate;

 6. Performing a urine based pregnancy test (women of child bearing potential only);

 7. Assessment of PASI; and

 8. Blood sampling for laboratory examination.

 An identification number will be allocated to the potential research participant following
 informed consent and provided that he or she meets the inclusion criteria and does not have
 an exclusion criterion to study entry. This identification number, together with the
 participant's initials, will act as a unique identifier for that participant.

 Baseline (Visit 2, Day 0) The potential research participant will return for the baseline
 visit within three weeks of the screening visit.

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant (Dermatology
 Life Quality Index (DLQI); EuroQol five item questionnaire (EQ-5D); Hospital Anxiety and
 Depression Scale (HADS); and Stanford HAQ 8-Item Disability Scale (HAQ-8) ;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Measurement of height, weight, blood pressure and heart rate;

 5. Performing a urine based pregnancy test (women of child bearing potential only);

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination. If the participant is willing a skin biopsy
 will be performed, using a sterile technique by an experienced physician, to determine
 skin immune cell number and skin pro-inflammatory protein level.

 If a participant is noted to score greater than 8 (out of 21) on either the anxiety or the
 depression components of the HADS, at this or any subsequent study visits, their General
 Practitioner (GP) will be advised of this and of the high likelihood of depressive/affective
 mental illness which may require treatment.

 The investigator, or authorised designee, will allocate then the research participant to a
 trial treatment arm using one of sixteen (8 per centre) prepared randomisation lists.

 The investigator, or authorised designee, will chose the appropriate list based on the
 participant's centre, HbA1c level (HbA1c < 38mmol/mol or ≥ 38mmol/mol), BMI level (BMI < 30
 kg/m2 or ≥ 30kg/m2) and previous response to NB-UVB (achieved remission within 25 exposures
 during most recent course of NBUVB or not). Those who have not been exposed previously to
 NBUVB will be placed in the "did not achieve remission within 25 exposures" group.

 For research participants allocated randomly to treatment arm A the investigator, or
 authorised designee, will ask the participant to bring back all used and unused Januvia®
 tablet packages at each study visit to enable a pill compliance check to be performed.

 1st Treatment visit (Visit 3, Week 3 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Assessment of study drug compliance (pill count);

 5. Measurement of weight, blood pressure and heart rate;

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination.

 2nd Treatment visit (Visit 4, Week 6 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Assessment of study drug compliance (pill count);

 5. Measurement of weight, blood pressure and heart rate;

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination.

 3rd Treatment visit (Visit 5, Week 12 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Assessment of study drug compliance (pill count);

 5. Measurement of weight, blood pressure and heart rate;

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination.

 4th Treatment visit (Visit 6, Week 24 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Assessment of study drug compliance (pill count);

 5. Measurement of weight, blood pressure and heart rate;

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination. If the participant is willing, and had a skin
 biopsy performed during visit 2, a skin biopsy will be performed, using sterile
 technique by an experienced physician, to determine skin immune cell number and skin
 pro-inflammatory protein level.

 1st Follow-Up visit (Visit 7, Week 30 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Measurement of weight, blood pressure and heart rate;

 5. Assessment of PASI; and

 6. Blood sampling for laboratory examination.

 End of Study visit (Visit 8, Week 36 +/- 7 days)

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Measurement of weight, blood pressure and heart rate;

 5. Performing a urine based pregnancy test (women of child bearing potential only);

 6. Assessment of PASI; and

 7. Blood sampling for laboratory examination.

 Early Withdrawal visit: All research participants who withdraw early from the study will be
 advised to agree to attend an early withdrawal visit.

 There will be a separate section in the CRF to be completed if the research participant
 withdraws early from the study before week 36.

 The following assessments will be performed:

 1. Completion of quality of life questionnaires by the research participant as detailed in
 Baseline Visit above;

 2. Recording of adverse events;

 3. Recording of changes in concomitant medication;

 4. Assessment of study drug compliance (pill count) if appropriate;

 5. Measurement of weight, blood pressure and heart rate;

 6. Performing a urine based pregnancy test (women of child bearing potential only);

 7. Assessment of PASI; and

 8. Blood sampling for laboratory parameters.

 The research participant's involvement in this study will end following the completion of the
 End of Study Visit (or Early Withdrawal visit if applicable). Once participants have
 completed their involvement in this study they will be provided with standard treatment by
 their usual healthcare providers.

 Adverse Events:

 Comprehensive assessments of any apparent toxicity experienced by the research participant
 will be performed throughout the course of the study from the time of participant's signature
 of informed consent.

 Adverse events (AEs) considered related to Study Drug at the End of Study Visit (or Early
 Withdrawal Visit, if applicable) will be followed until the participant is stable or the AE
 is resolved or the participant is lost to follow-up.

 Any medical condition, or clinically significant laboratory abnormality with an onset date
 before the Baseline Visit and not related to a protocol-associated procedure, is not an AE.
 It will be considered to be pre-existing.

 Complete and appropriate data on all Adverse Events experienced (observed, volunteered or
 elicited) during the reporting period will be reported on an ongoing basis in the Adverse
 Event Form pages of the Case Report Form. The investigator will classify the severity of an
 adverse event. The investigator will systematically assess the relationship of the adverse
 event to the investigational medicinal product.

 Reporting of Serious Adverse Events (SAEs) Information about all SAEs will be collected and
 recorded on the SAE Report Form. Each SAE must be reported by the Investigator, or an
 authorised designee, to the Sponsor within 24 hours of learning of its occurrence.

 Medical and scientific judgement will be exercised in deciding whether expedited reporting is
 appropriate in other situations, such as important medical events that may not be immediately
 life-threatening or result in death or hospitalisation, but may jeopardise the research
 participant or may require intervention to prevent one of the other outcomes listed in the
 definition above. These will be considered also serious.

 Justification of Population and Method of Estimation:

 We plan to enrol 120 research participants in total in the two sites. The primary objective
 of the research project is to determine the change in the psoriasis area and severity index
 (ΔPASI) during twenty four weeks of treatment with a dipeptidyl peptidase-4 inhibitor
 (Januvia®, 100mg daily or 50mg daily for participants with moderate kidney disease) in
 psoriasis patients undergoing narrow-band ultraviolet-B (NB-UVB) light therapy. This will be
 compared to the ΔPASI of psoriasis patients undergoing NB-UVB light therapy who are allocated
 randomly to not receive any additional treatment.

 Kleinpenning et al have determined previously the effect of two different NB-UVB light
 therapy regimens on the decrease in PASI three months after completion of a course of NB-UVB
 light therapy. Three months after cessation of NB-UVB light therapy the decrease in the PASI
 in those receiving an high-dose regimen was 5.93±4.1compared to baseline. This decrease in
 PASI was significantly less in the group receiving a low-dose regimen (4.14±2.96, p<0.05).

 Based on these data, and assuming a 33% dropout rate, we have calculated that we will require
 60 research participants (in each arm) to detect a greater than 33% difference in the ΔPASI
 with 80% power and a 5% significance level.

 Method of Randomisation:

 The unit of randomisation will be the individual research participant. After stratification
 by centre, by HbA1c level (HbA1c < 38mmol/mol or ≥ 38mmol/mol), BMI level (BMI < 30 kg/m2 or
 ≥ 30 kg/m2) and previous response to NB-UVB (achieved remission within 25 exposures during
 most recent course of NBUVB or not) 120 research participants will be assigned randomly, in a
 ratio of 1:1 using blocks of 2, to receive either:

 Januvia® tablets; OR No additional treatment.

 In order to achieve this we have prepared 8 randomisation lists using a web-based random
 generator programme. One copy of this document will be used for each centre.

 For each participant the investigator, or authorised designee, will chose the appropriate
 list and will add the participant's identifier to the list in chronological order. This list
 will be thereby used to determine the study treatment which the participant will receive.

 Random allocation will occur at visit 2 (baseline visit) once all screening procedures
 required at visit 1 (screening visit) have been completed, once it has been confirmed that
 the participant satisfies all inclusion and exclusion criteria and once the participant
 completes the three week run-in period.

 Identification numbers will be assigned chronologically in consecutive, ascending order.

 Independent Ethics Committee (IEC)/Institutional Review Board (IRB) Approval:

 Before initiating this study the Study Protocol, Summary of Product Characteristics (SPC),
 Patient Information Leaflet and Informed Consent Form, applicable advertising, and any other
 written information to be given to participants will be reviewed and approved by a properly
 constituted Institutional Review Board/Independent Ethics Committee (IEC/IRB). A signed and
 dated statement that all documents submitted for review have been approved by the IEC/IRB
 will be given to the Sponsor or designee before the study can commence at a site. The
 membership and the constitution of the IEC/IRB who approved the documents will be also
 supplied to the Sponsor or designee.

 Ethical Conduct of the Study:

 This study will be carried out in compliance with the Study Protocol and in accordance with
 the Sponsor/Contract Research Organisations (CROs) Standard Operating Procedures (SOPs).
 These are designed to ensure adherence to Good Clinical Practice (GCP) guidelines, as
 described in:

 International Conference on Harmonization of Technical Requirements for Registration of
 Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guidelines for Good Clinical
 Practice 1996.

 European Union (EU) CT Directive 2001/20/EC. GCP Commission Directive 2005/28/EC. Declaration
 of Helsinki, concerning medical research in humans (1964) including all amendments up to and
 including the 2008 revision.

 National laws. The investigator agrees, when signing the Study Protocol, to adhere to the
 instructions and procedures described in it and to the principles of GCP to which it
 conforms.

 The regulatory permission to perform the study will be obtained in accordance with applicable
 regulatory requirements. All ethical and regulatory approvals must be available before a
 patient is exposed to any study-related procedure, including screening tests to determine
 eligibility.

 Insurance:

 In case of any damage or injury occurring to a patient in association with the
 investigational medicinal product or their participation in the study, the sponsor has
 insurance which covers the liability of the sponsor, the investigator and other persons
 involved in the study in compliance with the laws of Ireland.

 All investigators are qualified and practicing physicians and are thus insured by the
 clinical indemnity scheme.
Inclusion Criteria:

 1. Have a diagnosis of generalized chronic plaque and/or guttate psoriasis;

 2. Are male and female patients aged between 18 and 75 years inclusive;

 3. Have a psoriasis area and severity index (PASI) greater than 7 despite use of topical
 therapies;

 4. Are due to undergo NB-UVB light therapy;

 5. Have not required systemic psoriasis therapy during the past eight weeks;

 6. Are unlikely to require systemic therapy for the duration of clinical trial
 involvement;

 7. Have a negative pregnancy test at screening (women of child bearing potential only);
 and

 8. Are willing to sign voluntarily a statement of informed consent to participate in the
 study.

 Exclusion Criteria:

 People with any of the following conditions will be excluded from the study:

 1. Photosensitive disorders (lupus erythematosis etc);

 2. Diabetes mellitus;

 3. Use of medications that can cause photosensitivity;

 4. Use of GLP-1 analogue therapy;

 5. Conditions that could be made worse by phototherapy (cataract, epilepsy, etc);

 6. Allergy or hypersensitivity to Januvia®;

 7. 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;

 8. Recent (within 8 weeks) receipt of NB-UVB light;

 9. Current or recent (within 8 weeks) use of systemic therapy for psoriasis;

 10. 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);

 11. 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;

 12. 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);

 13. Any other contraindications to Januvia® as stated in its SPC;

 14. 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;

 15. Any clinically significant chronic disease that might in the opinion of the
 investigator, interfere with the evaluations or preclude completion of the trial;

 16. A current or recent (within the past 4 weeks) acute serious illness, acute psychiatric
 illness or severe uncontrolled/unstable illness;

 17. Previous randomisation into this study;

 18. Concurrent participation in another clinical trial; and

 19. Participation in another clinical trial during the twelve weeks prior to study entry
 (i.e. screening visit).