Phase 2
Completed N=20
Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.
Source: ClinicalTrials.gov NCT01991197 ↗Enrolled (actual)
20
Serious AEs
15.0%
Results posted
May 2020
Primary outcomePrimary: The Change in the Psoriasis Area and Severity Index (PASI) From Baseline to 16 Weeks in Psoriasis Patients With Type 2 Diabetes Treated With Sitagliptin Compared to Patients Treated With Gliclazide. — 9.5; 9.4 score on a scale — p=0.648
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Change in the Psoriasis Area and Severity Index (PASI) From Baseline to 16 Weeks in Psoriasis Patients With Type 2 Diabetes Treated With Sitagliptin Compared to Patients Treated With Gliclazide. |
9.5; 9.4 | 0.648 |
| SECONDARY The Number of Patricipants in the Sitagliptin and Gliclazide Arms With Adverse Events at 32 Weeks. |
6; 10 | — |
| SECONDARY The Change in Quality of Life Scores From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
0.0; -1.0; 0.0; 0.0; -1; 0 | — |
| SECONDARY The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on Other Efficacy Endpoints. |
1; 1; 0; 0; 0; 0 | 1 |
| SECONDARY The Change in Levels of High Sensitivity C-reactive Protein From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
0; 8.4 | — |
| SECONDARY The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on the Serum Cytokine Tumour Necrosis Factor Alpha. |
0; 0 | — |
| SECONDARY The Change in PASI From Baseline to 32 Weeks in Psoriasis Patients With Type 2 Diabetes Treated With Sitagliptin Compared to Patients Treated With Gliclazide. |
3; 1.8 | 0.128 |
| SECONDARY The Change in Weight From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
-0.5; -0.6 | — |
| SECONDARY The Change in Levels of Systolic Blood Pressure From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
4; -9 | — |
| SECONDARY The Change in Levels of Serum Glucose From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
-0.2; -0.1 | — |
| SECONDARY The Change in Levels of Total Cholesterol From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms. |
0.1; -0.1 | — |
| SECONDARY The Effects of Treatment With Sitagliptin and Treatment With Gliclazide From Baseline to 16 Weeks on Serum Levels Interleukin-23. |
0; 0 | — |
| SECONDARY The Effects of Treatment With Sitagliptin and Treatment With Gliclazide From Baseline to 16 Weeks on Serum Levels Interleukin-17. |
0; 0 | — |
| SECONDARY The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on the Change in Serum Leptin From Baseline to 16 Weeks. |
-0.07; 0.43 | — |
Eligibility Criteria
Inclusion Criteria
People who satisfy all of the following may be included in the study:
- Have a diagnosis of generalized chronic plaque and/or guttate psoriasis;
- Are male or female aged between 18 and 75 years inclusive;
- Have a psoriasis area and severity index (PASI) greater than 7;
- Have a diagnosis of type 2 diabetes;
- Have a glycated haemoglobin (HbA1c) level between 48mmol/mol and 69mmol/mol;
- 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;
- Have a negative pregnancy test at screening (women of child bearing potential only); and
- 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:
- Allergy or hypersensitivity to sitagliptin (Januvia®) or gliclazide (Diamicron®);
- Current or recent (within 8 weeks) receipt of phototherapy;
- Type 1 diabetes;
- 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;
- 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);
- 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;
- 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);
- Any other contraindications, as stated in the SPCs for sitagliptin (Januvia®) or gliclazide (Diamicron®);
- 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;
- Any clinically significant chronic disease that might, in the opinion of the investigator, interfere with the evaluations or preclude completion of the trial;
- Any current or recent (within the past 4 weeks) acute serious illness, acute psychiatric illness or severe uncontrolled/unstable illness;
- Previous randomisation into this study;
- Concurrent participation in another clinical trial; and
- Participation in another clinical trial during the twelve weeks prior to study entry (i.e.
screening visit).
Data sourced from ClinicalTrials.gov (NCT01991197). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.