Amyotrophic Lateral Sclerosis and the Innate Immune System
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 375
- 试验地点
- 8
- 主要终点
- Complement activity
研究概览
简要总结
Amyotrophic Lateral Sclerosis (ALS) is an aggressive, deadly disease. ALS leads to destruction of the neural pathways which control the conscious movements of the muscles. This destruction leads to muscular dystrophy with increasing difficulties in moving, breathing, swallowing, and speaking. In the last phase of an ALS patient's life it is necessary with respiratory therapy in order to breathe. In average an ALS patient lives 3 years from the time he or she gets the diagnose.
The cause of the disease is still unknown and there is currently no treatment which can stop the progression of the disease. Former clinical studies have indicated that the innate immune system and in particular the complement system plays a significant role in the progression of ALS. The complement system, which is activated in cascades, is part of the innate system but participates in the innate as well as the acquired immune system. Former clinical trials have been characterized by limited knowledge about both the complement system as well as to how it is measured.
Today it is possible to measure directly on the different components of the complement system and to understand its contribution to the overall immune response. It is also possible today to detect defects of the complement system. All these progressions are the foundation for this project which is carried out in close cooperation with one of the world's leading researchers in the complement system, professor Peter Garred from Rigshospitalet.
The aim is to make a national research project about ALS in order to investigate the role of the innate immune system, and especially the complement system, in patients with ALS.
In the long term the hope is, that this will lead the way to a targeted and effective medical treatment to the people affected by this grave disease.
详细描述
Amyotrophic lateral sclerosis (ALS) is a progressive, deadly, neurodegenerative disease which affects the upper and lower motor neurons. This leads to profound muscular dystrophy, hyperreflexia, fasciculations and paresis of the bulbar as well as the skeletal musculature. ALS causes increasing physical fatigue and the patients soon become bedridden and respiratory insufficient.The diagnosis ALS is made according to the El Escorial revisited. Often clinical and neurophysiological tests must be repeated (1-4).
In Denmark the incidence of ALS is 1-2/100.000 and the prevalence is 4-6/100.000. The average survival time from the time of the diagnosis is 3 years but with great variance. (5+6)
Today the pathogenesis is still unknown and no treatment can stop the progression of ALS. Treatment with riluzole seems to prolong the median time of survival for 2 or 3 months (7).
Most likely, a future medical treatment requires a better understanding of the pathogenesis as well as the pathophysiology of ALS. This present study aims to do so based on the hypothesis that ALS partially or fully is caused by complement activation.
The complement system is a complex system consisting of proteins in plasma as well as membrane bound proteins which together complement the antibody-based immune system. The complement system is a self-perpetuating cascade system which is activated through different pathways. It works by opsonisation where complement proteins bind to microorganisms to activate and target granulocytes, monocytes and macrophages. The complement system also causes cytolysis of microorganisms via MAC (membrane attack complex) by activation of the mast cells. It also inactivates and eliminates burned out immune complexes as well as performing apoptotic renovation.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For ALS group:Diagnosed with the diagnose category "certain ALS" or "likely ALS according to the El Escorial rev. diagnose criteria
- •For Neurological control group: Referred to neurological department to be examined for acute or chronic headache or referred to get a lumbar perfusion test performed.
排除标准
- •For all groups (Clinical study 2-3): permanent contraindication for having a lumbar puncture performed
- •For Neurological control group: Known with chronic inflammatory disease or autoimmune disease.
- •For healthy control group (clinical study 1): Known with any disease
- •For healthy control group (clinical study 1): Taking daily medication
- •For Neurologically healthy control group (Clinical study 2): Known with neurological disease
- •For Neurologically healthy control group (Clinical study 2): Known with chronic inflammatory disease or autoimmune disease.
结局指标
主要结局
Complement activity
时间窗: 0-10 year
The complement activity (measured by haemolytic capacity, complement-activation potential and specific mediators) in ALS patients and compared with 2 control groups.
次要结局
- Subcomponents of the complement cascade(0-10 years)
- Cytokines present in the blood(0-10 years)
- Quantitatively and qualitatively description of ALS muscle fibers.(0-3 years)
- Acut phase reactants(0-10 years)
- Regression analysis(0-10 years)
- Indirect profiling of inflammatory proteins present in the blood(0-10 years)
- Inactivation of the complement system(0-2 years)
- Complement activity in the neuromuscular junctions of ALS patients. (Clinical trial 4)(0-3 years)
研究者
Anne-Lene Kjældgaard
Ph.d.-student, MD
Rigshospitalet, Denmark