Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.
Condition: Psoriasis; Type 2 Diabetes Mellitus
MeSH terms: Psoriasis; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Gliclazide; Sitagliptin matched placebo; Gliclazide matched placebo capsule
Intervention description: Week 0-16: Two 50mg tablets (or one 50mg tablet for participants with moderate kidney disease) once daily for 16 weeks during the double-blind phase.
Week 16-32: Then two 50mg tablets (or one 50mg tablet for participants with moderate kidney disease) once daily for 16 weeks during the open-label phase of the trial.; Double-blind phase (week 0-16):
One 80mg capsule once daily for 4 weeks. The if no severe hypoglycaemic episodes one 80mg capsule twice daily for 4 weeks.
Then if no severe hypoglycaemic episodes two 80mg capsules twice daily for 8 weeks.; Week 0-16: Two tablets (or one tablet for those with moderate kidney disease) daily for 16 weeks during the double-blind phase.; Double-blind phase (week 0-16):
One capsule daily for 4 weeks. Then if no severe hypoglycaemic episodes one capsule twice daily for 4 weeks. Then if no severe hypoglycaemic episodes two capsules twice daily for 8 weeks.
Intervention MeSH terms: Sitagliptin Phosphate; Gliclazide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Psoriasis; Type 2 Diabetes; Dipeptidyl peptidase-4 inhibition; Sitagliptin; Gliclazide; Psoriasis area and severity index

Summary:

      The primary purpose of this study is to determine if sitagliptin (Januvia®) improves
      psoriasis severity after 16 weeks of treatment in 20 participants with both psoriasis and
      type 2 diabetes mellitus. We will compare the change in psoriasis severity in 20 participants
      treated with Januvia® to 20 participants treated with 16 weeks of a comparator drug
      (gliclazide, Diamicron®). Participants will be recruited from two centres and after a 4 week
      washout period will be followed prospectively for 36 weeks. Participants will be stratified
      by centre, psoriasis severity and obesity status after which they will be randomly allocated
      to Arm A or Arm B. Participants will be treated with either Januvia® and Diamicron® matched
      placebo capsules (Arm A), or Diamicron® and Januvia® matched placebo tablets (Arm B) for 16
      weeks and then proceed to an open-label phase where all participants will receive Januvia®
      for a further 16 weeks.

      Both the research participants and the investigators will be unaware of the trial arm to
      which the research participant has been allocated (double-blind study). Research participants
      will be prohibited from making any changes to the dose of medications used to treat
      psoriasis. If a participant's plasma glycated haemoglobin level (HbA1c) (reflects a
      participant's glucose control over the previous 3 months) is above 64mmol/mol eight weeks
      after commencing one of the study investigational medicinal products (IMPs) insulin therapy
      will be used to improve glycaemic control.

      Participants will be assessed at 9 study visits over 40 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 3 visits).

      The following endpoints will be analysed:

      Changes in psoriasis severity at 16 and 32 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.

      We hypothesize that sitagliptin therapy decreases psoriasis severity.
    

Eligibility criteria:

        Inclusion Criteria:

        People who satisfy all of the following may be included in the study:

          1. Have a diagnosis of generalized chronic plaque and/or guttate psoriasis;

          2. Are male or female aged between 18 and 75 years inclusive;

          3. Have a psoriasis area and severity index (PASI) greater than 7;

          4. Have a diagnosis of type 2 diabetes;

          5. Have a glycated haemoglobin (HbA1c) level between 48mmol/mol and 69mmol/mol;

          6. Are able and willing to stop sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitor
             and glucagon-like peptide-1 (GLP-1) analogue therapy for the duration of the study;

          7. Have a negative pregnancy test at screening (women of child bearing potential only);
             and

          8. Are willing to voluntarily sign 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. Allergy or hypersensitivity to sitagliptin (Januvia®) or gliclazide (Diamicron®);

          2. Current or recent (within 8 weeks) receipt of phototherapy;

          3. Type 1 diabetes;

          4. 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/1.73 m2;

          5. 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);

          6. 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;

          7. 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 (IU)/L (greater than three times the upper limit of the normal reference range);

          8. Any other contraindications, as stated in the SPCs for sitagliptin (Januvia®) or
             gliclazide (Diamicron®);

          9. 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;

         10. Any clinically significant chronic disease that might, in the opinion of the
             investigator, interfere with the evaluations or preclude completion of the trial;

         11. Any current or recent (within the past 4 weeks) acute serious illness, acute
             psychiatric illness or severe uncontrolled/unstable illness;

         12. Previous randomisation into this study;

         13. Concurrent participation in another clinical trial; and

         14. Participation in another clinical trial during the twelve weeks prior to study entry
             (i.e.

        screening visit).