Dipeptidyl Peptidase-4 Inhibition and Narrow-band Ultraviolet-B Light in Psoriasis (DINUP): A Randomised Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- The change in PASI during treatment with sitagliptin for participants with psoriasis undergoing NB-UVB light therapy compared to psoriasis patients undergoing NB-UVB light therapy who are allocated randomly to not receive any additional treatment.
研究概览
简要总结
The primary purpose of this study is to determine if sitagliptin (Januvia®) improves psoriasis severity after 24 weeks of treatment in 60 participants with psoriasis who do not have type 2 diabetes mellitus, and who are due to receive a course of narrowband ultraviolet-B phototherapy (NB-UVB). The investigators will compare the change in psoriasis severity in 60 participants treated with both sitagliptin and NB-UVB to 60 participants treated with NB-UVB alone. Participants will be recruited from two centres and after a 3 week run-in period will be followed prospectively for 36 weeks. Participants will be stratified by centre, plasma glycated haemoglobin level (HbA1c), obesity status and previous response to NB-UVB, after which they will be randomly allocated to Arm A or Arm B. Participants will be treated with either sitagliptin for 24 weeks and NB-UVB (Arm A), or NB-UVB alone (Arm B).
Both the research participants and the investigators will be aware of the trial arm to which the research participant has been allocated randomly (open-label study). Research participants are prohibited from using systemic psoriasis therapy for the duration of their trial involvement.
Participants will be assessed at 8 study visits over 39 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 2 visits).
The following endpoints will be analysed:
Changes in psoriasis severity at 24 and 36 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.
The investigators hypothesize that sitagliptin therapy decreases psoriasis severity.
详细描述
Background:
Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's population. It is characterised by keratinocyte hyperproliferation, by aberrant keratinocyte differentiation and by cutaneous inflammation.
Dipeptidyl peptidase-4 (DPP-4) is expressed on keratinocytes and its activity is upregulated in psoriasis. DPP-4 inhibition suppresses keratinocyte proliferation and restores partially keratinocyte differentiation. The main site of DPP-4 activity is cluster of differentiation antigen 26 (CD26). CD26 is a marker of T cell activation and is a key molecule in the pathogenesis of autoimmune diseases. One case of DPP-4 inhibitor therapy improving psoriasis severity has been reported.
Agents used to treat psoriasis target commonly the underlying inflammation. C-reactive protein (CRP) is a sensitive, systemic marker of inflammation. In people with type 2 diabetes (T2DM) DPP-4 inhibitor therapy decreases CRP concentrations. Serum CRP concentrations correlate with psoriasis severity and interventions that decrease the CRP concentration may decrease also psoriasis severity. Medications that improve insulin resistance may decrease also systemic inflammation and improve psoriasis. We have shown previously, in psoriasis patients without T2DM (both lean and obese), that the fasting insulin concentration and the homeostatic model of insulin resistance (measures of insulin resistance) correlate strongly with the psoriasis area and severity index (PASI, a measure of psoriasis severity: r=0.48, p<0.001; r=0.49, p<0.001).
DPP-4 inhibitors prevent also the degradation of insulin secretagogues, such as glucagon-like peptide-1 (GLP-1), thereby ameliorating hyperglycaemia without causing hypoglycaemia. Due to this effect DPP-4 inhibitors are effective for the treatment of T2DM. Other interventions which increase GLP-1 receptor activation, such as roux-en-Y gastric bypass surgery and GLP-1 analogue therapy, can improve also psoriasis severity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of generalized chronic plaque and/or guttate psoriasis;
- •Are male and female patients aged between 18 and 75 years inclusive;
- •Have a psoriasis area and severity index (PASI) greater than 7 despite use of topical therapies;
- •Are due to undergo NB-UVB light therapy;
- •Have not required systemic psoriasis therapy during the past eight weeks;
- •Are unlikely to require systemic therapy for the duration of clinical trial involvement;
- •Have a negative pregnancy test at screening (women of child bearing potential only); and
- •Are willing to sign voluntarily a statement of informed consent to participate in the study.
排除标准
- •People with any of the following conditions will be excluded from the study:
- •Photosensitive disorders (lupus erythematosis etc);
- •Diabetes mellitus;
- •Use of medications that can cause photosensitivity;
- •Use of GLP-1 analogue therapy;
- •Conditions that could be made worse by phototherapy (cataract, epilepsy, etc);
- •Allergy or hypersensitivity to Januvia®;
- •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/1.73m2;
- •Recent (within 8 weeks) receipt of NB-UVB light;
- •Current or recent (within 8 weeks) use of systemic therapy for psoriasis;
- •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/L (greater than three times the upper limit of the normal reference range);
- •Any other contraindications to Januvia® as stated in its SPC;
- •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;
- •A 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).
研究组 & 干预措施
A
Sitagliptin 100mg once daily orally or 50mg once daily for participants with moderate kidney disease for 24 weeks and narrowband ultraviolet-B (NBUVB) phototherapy.
NBUVB light therapy is continued until the participants' psoriasis clears (<1% body surface area involved).
干预措施: Sitagliptin (Januvia) (Drug)
结局指标
主要结局
The change in PASI during treatment with sitagliptin for participants with psoriasis undergoing NB-UVB light therapy compared to psoriasis patients undergoing NB-UVB light therapy who are allocated randomly to not receive any additional treatment.
时间窗: 24 weeks
次要结局
- The incidence of adverse events in the patients treated with sitagliptin and in the patients receiving no additional treatment(24 and 36 weeks)
- The change in DLQI in patients receiving treatment with sitagliptin compared to the change in DLQI in patients receiving no additional treatment.(24 and 36 weeks)
- The change in PASI over 36 weeks in patients treated with sitagliptin compared to patients receiving no additional treatment.(36 weeks)
- The change in blood pressure in patients treated with sitagliptin compared to patients receiving no additional treatment.(24 and 36 weeks)
- The incidence of discontinuation of the study investigational medicinal product (IMP).(24 weeks)
- The change in serum cytokines in patients treated with sitagliptin compared to patients receiving no additional treatment.(24 and 36 weeks)
- The change in HADS in patients receiving treatment with sitagliptin compared to the change in HADS in patients receiving no additional treatment.(24 and 36 weeks)
- The change in HAQ8 in patients receiving treatment with sitagliptin compared to the change in HAQ8 in patients receiving no additional treatment.(24 and 36 weeks)
- The change in EQ-5D in patients receiving treatment with sitagliptin compared to the change in EQ-5D in patients receiving no additional treatment.(24 and 36 weeks)
- The incidence of achievement of a greater than 50% reduction in PASI from baseline (PASI-50) in patients receiving sitagliptin and in patients receiving no additional treatment.(36 weeks)
- The incidence of achievement of a greater than 75% reduction in PASI from baseline (PASI-75) in patients receiving sitagliptin and in patients receiving no additional treatment.(36 weeks)
- The incidence of achievement of a greater than 90% reduction in PASI from baseline (PASI-90) in patients receiving sitagliptin and in patients receiving no additional treatment.(36 weeks)
- The dosage of narrow-band ultraviolet-B light received by patients receiving sitagliptin and by patients receiving no additional treatment.(36 weeks)
- The number of exposures of narrow-band ultraviolet-B light received by patients receiving sitagliptin and by patients receiving no additional treatment.(36 weeks)
- The proportion of patients who relapse (PASI greater than 50% of original value) within 36 weeks of commencement of NBUVB light therapy in patients receiving sitagliptin and in patients receiving no additional treatment.(36 weeks)
- The times taken to achieve PASI-50, PASI-75, PASI-90 and relapse in patients receiving sitagliptin and in patients receiving no additional treatment.(36 weeks)
- The change in glycaemic measures in patients treated with sitagliptin compared to patients receiving no additional treatment.(24 and 36 weeks)
- The change in lipid fractions in patients treated with sitagliptin compared to patients receiving no additional treatment.(24 and 36 weeks)
- The change in weight in patients treated with sitagliptin compared to patients receiving no additional treatment.(24 and 36 weeks)