Long-term Characterization of Lipoprotein Apheresis Technologies for Individual Device Adaption (LOLIDA)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Identification of new biomarkers for individualized assignment of lipoprotein apheresis technology
研究概览
简要总结
Lipoprotein apheresis is often applied as the final treatment of patient with severe and medication resistant dyslipidemia and progressive atherosclerosis. The high effectiveness of lipoprotein apheresis to improve the patient's metabolic situation and thereby strongly minimize the incidence of cardiovascular events was confirmed by a variety of studies.
While in the past years, mostly patients with severe homo- or heterozygous familial hypercholesterolemia (FH) or otherwise highly elevated LDL-cholesterol were subjected to lipoprotein apheresis, currently the major indication for lipoprotein apheresis is a critical elevated plasma level of lipoprotein (a) [Lp(a)] in patients with severe cardiovascular events. Even if it is now widely accepted that Lp(a) is an independent risk factor for cardiovascular diseases due to its pro-atherogenic potential, the exact molecular mechanisms by which Lp(a) contributes to the atherosclerotic process remain unclear. Despite rigorous reduction of plasma Lp(a)-levels during lipoprotein apheresis newly occurring cardiovascular events cannot prevented in all patients. Specific pleiotropic effects of apheresis technologies are supposed to be critically involved in the clinical outcome. By measurement of a wide variety of cardio-metabolic biomarkers playing a role in inflammation, endothelial dysfunction, lipid metabolism or blood pressure regulation during repeated Lp(a) lowering by various apheresis methods may allow the identification of clusters of risk factors determining clinical outcome and give the biological basement for an optimized individual lipoprotein apheresis therapy.
详细描述
Aims The aim of the proposed project is the investigation of Lp(a) kinetics in patients under regular lipoprotein apheresis with regard to short- and long-term changes in diverse clinical parameter contributing to atherogenesis by applying different LA methods. The expected gain of knowledge might result in an improvement of patient stratification and the individual assignment to a well-tolerated and optimal apheresis procedure, which is essential for therapy outcome and improvement of the patient's life quality.
Specific questions Depending on the apheresis procedure, does the repeated use of lipoprotein apheresis therapy in patients with pathological high Lp(a) plasma concentration cause reproducible and stable changes in biomarkers of cardial dysfunction, inflammatory state, oxidative stress, endothelial dysfunction, and cardial fibrosis?
Is there an association between Lp(a)- and biomarker dynamics during long-term lipoprotein apheresis?
It is possible to identify high-risk cluster of biomarkers in patients with newly occurring cardio-vascular events after the onset of lipoprotein apheresis?
(I) Set up of examination cohorts and basal characterization of the patients
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria for lipoprotein apheresis in accordance with regulations of the German Federal Joint Committee of physicians and medical insurance companies (G-BA; Gemeinsamer Bundesausschuss der Ärzte und Krankenkassen) are either:
- •homozygous familial hypercholesterolemia or
- •severe hypercholesterolemia in patients after 12 month of dietary intervention and maximal lipid-lowering drug therapy with regard on the overall risk profile of the patient or
- •Lp(a) levels > 120 nmol/L in patients with progressive cardiovascular disease after unsuccessful intervention with established methods of treatment
- •Mandatory for inclusion of patients for lipoprotein apheresis is a comprehensive cardiological, angiological and lipidological pre-examination.
- •(Deutsches Ärzteblatt 100 (2003), 1595; Deutsches Ärzteblatt 105 (2008), 1778)
排除标准
- •Patients after transplantation
- •Immunosuppressive therapy (including intake of glucocorticoids within four weeks prior to sample collection)
- •uncontrolled arterial hypertension (>180/110 mm Hg)
- •acute malignant and infectious diseases
- •liver disease (gamma-GT > 1.8 μmol/L×s, ALAT > 1.5 μmol/L×s),
- •severe renal dysfunction (GFR < 30 ml/min per 1.73 m2)
- •hypersensitivity against heparin
- •participation in another study
结局指标
主要结局
Identification of new biomarkers for individualized assignment of lipoprotein apheresis technology
时间窗: 10 years
Characterization of short- and long-term effects of repeated lipoprotein apheresis by dextran sulfate absorption (LIPOSORBER® D - Kaneka Pharma Europe NV), lipid filtration (Octo Nova®, Diamed Medizintechnik), direct absorption of lipoproteins (DALI®; ADS 4008, Fresenius), and TheraSorb™ (Miltenyi Biotec GmbH, Germany) on cardio-metabolic risk factors, including biomarkers of heart failure, inflammation, oxidative stress, endothelial dysfunction and fibrosis.
次要结局
- Recordings of newly manifested cardiovascular events(10 years)