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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 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: August 25, 2014
Last verified: August 2014
  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: April 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, 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: August 25, 2014
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:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Psoriasis
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Skin Diseases
Skin Diseases, Papulosquamous
Gliclazide
Hypoglycemic Agents
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014