Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.

This study is not yet open for participant recruitment.
Verified November 2013 by University College Dublin
Sponsor:
Information provided by (Responsible Party):
Maeve Lynch, University College Dublin
ClinicalTrials.gov Identifier:
NCT01991197
First received: November 10, 2013
Last updated: November 17, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Psoriasis
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Gliclazide
Drug: Sitagliptin matched placebo
Drug: Gliclazide matched placebo capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.

Resource links provided by NLM:


Further study details as provided by University College Dublin:

Primary Outcome Measures:
  • The change in the psoriasis area and severity index (PASI) in psoriasis patients with type 2 diabetes treated with sitagliptin and this change in PASI will be compared to patients treated with gliclazide. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Dosage: Sitagliptin: 100mg daily, or 50mg daily for participants with moderate kidney disease Gliclazide: 80-320mg daily


Secondary Outcome Measures:
  • The effects of treatment with sitagliptin and treatment with gliclazide on adverse events. [ Time Frame: 16 weeks and 32 weeks ] [ Designated as safety issue: Yes ]

    Dosage: Sitagliptin: 100mg daily, or 50mg daily for participants with moderate kidney disease Gliclazide: 80-320 mg daily.

    Secondary outcomes:

    1. Incidence of adverse events;
    2. Incidence of discontinuation of one of the study investigational medicinal products (IMPs).

  • The effects of treatment with sitagliptin and treatment with gliclazide on quality of life scores. [ Time Frame: 16 weeks and 32 weeks ] [ Designated as safety issue: No ]

    Secondary outcome:

    c. Changes in quality of life scores (DLQI, EQ-5D, HADS, and HAQ-8).


  • The effects of treatment with sitagliptin and treatment with gliclazide on other efficacy endpoints. [ Time Frame: 16 weeks and 32 weeks ] [ Designated as safety issue: No ]

    Secondary outcomes:

    d. Incidence of achievement of a greater than 50% reduction in PASI from baseline (PASI-50); e. Incidences of PASI-75 and PASI-90; and f. Times taken to achievement of PASI-50, PASI-75 and PASI-90.


  • The effects of treatment with sitagliptin and treatment with gliclazide on cardiovascular profiles. [ Time Frame: 16 weeks and 32 weeks ] [ Designated as safety issue: No ]

    Secondary outcome:

    g. Changes in levels of cardiovascular disease risk factors (blood pressure, glycaemic measures, lipid fractions, weight etc).


  • The effects of treatment with sitagliptin and treatment with gliclazide on laboratory parameters. [ Time Frame: 16 weeks and 32 weeks ] [ Designated as safety issue: No ]

    Secondary outcomes:

    h. Changes in serum concentrations of cytokines (CRP, interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα) etc); i. Changes in serum concentrations of hormones (GLP-1, peptide YY (PYY) etc); and j. Changes in peripheral blood mononuclear cell expression of immune proteins (IL-6, TNFα, IL-10, IL-27 etc).


  • The change in PASI in psoriasis patients with type 2 diabetes treated with sitagliptin and this change in PASI will be compared to patients treated with gliclazide. [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Dosage: Sitagliptin: 100mg daily, or 50mg daily for participants with moderate kidney disease Gliclazide: 80-320mg daily


Other Outcome Measures:
  • The effect of treatment with sitagliptin and with gliclazide on the change in skin levels and expression of cells, hormones, receptors, enzymes and immune proteins (in a sub-group of participants willing to undergo skin biopsies). [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Dosage: Sitagliptin: 100mg daily, or 50mg daily for participants with moderate kidney disease Gliclazide: 80-320mg daily

  • Genetic, and/or epigenetic, profile that predicts best response to DPP-4 inhibitor therapy. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    DPP-4 inhibitor: sitagliptin


Estimated Enrollment: 40
Study Start Date: February 2014
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin

Double blind phase (week 0-16):

Sitagliptin two 50mg tablets (or one 50mg in participants with moderate kidney disease) once daily for 16 weeks.

Placebo Comparator: Gliclazide matched placebo One gliclazide matched placebo capsule daily for 4 weeks. If no severe hypoglycaemic episodes one gliclazide matched placebo capsule twice daily for 4 weeks. If no severe hypoglycaemic episodes two gliclazide matched placebo capsules twice daily for 8 weeks.

Open-label phase (week 16-32):

Sitagliptin two 50mg tablets (or one 50mg in participants with moderate kidney disease) once daily for 16 weeks.

Drug: Sitagliptin

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.

Other Name: Januvia®
Drug: Gliclazide matched placebo capsule

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.

Active Comparator: Gliclazide

Double-blind phase (week 0-16):

Gliclazide 80mg once daily for 4 weeks Then if no severe hypoglycaemic episodes increase to Gliclazide 80mg twice daily for 4 weeks.

Then if no severe hypoglycaemic episodes increase to Gliclazide 160mg twice daily for 8 weeks Placebo Comparator: Sitagliptin matched placebo Two tablets (or one tablet in participants with moderate kidney disease) once daily for 16 weeks.

Open-label phase (week 16-32):

Sitagliptin two 50mg tablets (or one 50mg in participants with moderate kidney disease) once daily for 16 weeks.

Drug: Sitagliptin

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.

Other Name: Januvia®
Drug: Gliclazide

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.

Other Name: Diamicron
Drug: Sitagliptin matched placebo
Week 0-16: Two tablets (or one tablet for those with moderate kidney disease) daily for 16 weeks during the double-blind phase.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01991197

Contacts
Contact: Maeve Lynch, MB BCh BAO +353873580487 lynchmaeve@yahoo.ie

Locations
Ireland
The Adelaide and Meath Hospital Not yet recruiting
Dublin 24, Ireland
Contact: Anne-Marie Tobin, MB BCh BAO    +353-1-4142081    tobin.annemarie@gmail.com   
Sub-Investigator: Anne-Marie Tobin, MB BCh BAO PhD         
UCD Clinical Research Centre, St Vincent's University Hospital, Not yet recruiting
Dublin 4, Ireland
Contact: Peter Doran, BSc PhD    +353 1 7164582    peter.doran@ucd.ie   
Principal Investigator: Brian Kirby, MB BCh BAO MD         
Sub-Investigator: Maeve Lynch, MB BCh BAO         
Sub-Investigator: Tomas Ahern, MB BCh BAO         
Sub-Investigator: Donal O'Shea, MB BCh BAO         
Sub-Investigator: Anne-Marie Tobin, MB BCh BAO PhD         
Sponsors and Collaborators
University College Dublin
Investigators
Principal Investigator: Brian Kirby, MB BCh BAO MD UCD Clinical Research Centre, St Vincent's University Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Maeve Lynch, MD student, Medical Doctor, University College Dublin
ClinicalTrials.gov Identifier: NCT01991197     History of Changes
Other Study ID Numbers: DPIDM-2012-01, 2012-005505-51
Study First Received: November 10, 2013
Last Updated: November 17, 2013
Health Authority: Ireland: Irish Medicines Board

Keywords provided by University College Dublin:
Psoriasis
Type 2 Diabetes
Dipeptidyl peptidase-4 inhibition
Sitagliptin
Gliclazide
Psoriasis area and severity index

Additional relevant MeSH terms:
Hypoglycemic Agents
Diabetes Mellitus
Diabetes Mellitus, Type 2
Psoriasis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Skin Diseases, Papulosquamous
Skin Diseases
Sitagliptin
Gliclazide
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014