Phase 2 N=20 Randomized Quadruple-blind Treatment

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

Psoriasis · Type 2 Diabetes Mellitus

Bottom Line

View on ClinicalTrials.gov: NCT01991197 ↗

Enrolled (actual)

Serious AEs

15.0%

Results posted

May 2020

Primary outcome: 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 score on a scale — p=0.648

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Sitagliptin (Drug); Gliclazide (Drug); Sitagliptin matched placebo (Drug); Gliclazide matched placebo capsule (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University College Dublin
Primary completion: Jan 2016

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	—

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:

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).

View full record on ClinicalTrials.gov →

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.