Effects of Treatment With Biological Agents on Endothelial Glycocalyx,Arterial Elastic Properties, Coronary Flow, Myocardial Deformation and Twisting in Psoriasis. Comparative Study With Patients With CAD or Untreated Hypertension.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on endothelial function in psoriasis
研究概览
简要总结
Psoriasis has been associated with an increasing risk for atherosclerosis. The investigators investigated whether surrogate markers of subclinical atherosclerosis, vascular dysfunction and myocardial dysfunction are impaired in patients with psoriasis compared to normal controls ,coronary artery disease patients and untreated hypertension subjects. The investigators also examined the effect of treatment with biological vs no biological agents on vascular and LV function in psoriasis.
详细描述
The investigators will compare patients with psoriasis with age and sex matched normal controls as well as patients with angiographically documented CAD and patients with untreated hypertension (HYP) used as positive control groups
Patients with psoriasis (PS) will be randomized to receive an anti-tumor necrosis-a (TNF-a) ,an anti- interleukin 12/23 regimen, an interleukin 17A antagonist, apremilast (inhibitor of phosphodiesterase-4) or a cyclosporine regimen.
The anti-TNF-agent, Etanercept will be given at a dose 50mg twice weekly for 12 weeks and after then once weekly.
The anti-IL12/23 regimen, Ustekinumab will be given at a dose 45 mg at the first visit, at 4 weeks and every 12 weeks if body weight is up to 90 kgr. For body weight >90kgr dose will be adjusted accordingly.
The IL-17A antagonist regimen namely secukinumab 300 mg SC at weeks 0, 1, 2, 3, and 4 and 300 mg SC once monthly afterwards Apremilast will be given at a dose of 30mg orally twice daily Cyclosporine will be administered at a dose 2.5-3mg/kgr daily.
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •patients with psoriasis
- •Age and sex matched patients with CAD, with untreated hypertension and healthy subjects
排除标准
- •for psoriasis patients were presence of wall motion abnormalities and ejection fraction ≤ 50%, psoriatic arthritis, history of acute coronary syndrome, familial hyperlipidemia, insulin dependent-diabetes mellitus, chronic obstructive pulmonary disease or asthma, moderate or severe valvular heart disease, primary cardiomyopathies and malignant tumors. CAD was excluded in psoriasis patients by absence of clinical history, angina and reversible myocardial ischemia, as assessed by dobutamine stress echocardiography or thallium scintigraphy
- •regarding the group of CAD patients, we only included patients without history of ST elevation myocardial infarction in order to exclude the presence of transmural scar compromising myocardial function indices. Thus, CAD patients with wall motion abnormalities and ejection fraction of ≤ 50% were excluded. In addition, exclusion criteria, were history of acute coronary syndrome without ST-segment elevation within the last year, familial hyperlipidemia, insulin dependent-diabetes mellitus, chronic obstructive pulmonary disease or asthma, moderate or severe valvular heart disease, primary cardiomyopathies and malignant tumor
- •in normal controls, CAD was excluded by the presence of normal ECG, absence of clinical history and absence of reversible ischemia by means of treadmill test or dobutamine stress echocardiography
研究组 & 干预措施
Anti-TNFa regimen
Etanercept 50 mg
干预措施: etanercept (Drug)
Anti IL12/23 regimen
ustekinumab 45 mg
干预措施: ustekinumab (Drug)
Cyclosporine regimen
Cyclosporine 2.5-3 mg/kg
干预措施: cyclosporine (Drug)
anti-interleukin 17 A regimen
secukinumab 300 mg
干预措施: Secukinumab (Drug)
inhibitor of phosphodiesterase-4
apremilast 30mg
干预措施: Apremilast (Drug)
结局指标
主要结局
Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on endothelial function in psoriasis
时间窗: 12 weeks
Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on endothelial function as assessed by flow mediated dilatation of the brachial artery, coronary flow reserve and endothelial glycocalyx thickness
Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on vascular function in psoriasis
时间窗: 12 weeks
Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on vascular function as assessed by pulse wave velocity, augmentation index and central aortic blood pressure,
Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on cardiac function in psoriasis
时间窗: 12 weeks
Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23 ,anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on cardiac function as assessed by longitudinal myocardial deformation, twisting and untwisting of the left ventricle
次要结局
- Effects of anti-inflammatory treatment on prognosis for major adverse cardiovascular events(4-year follow-up)
- Differences and similarities in vascular function between psoriasis and control groups(0 and 12 weeks)
- Differences and similarities in cardiac function between psoriasis and control groups(0 and 12 weeks)
- Differences and similarities in endothelial function between psoriasis and control groups(0 and 12 weeks)
研究者
Ignatios Ikonomidis
Assistant Professor in Cardiology
University of Athens