Double-blinded, Randomized, Sham-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-acute COVID-19 CFS (PACS-CFS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale
研究概览
简要总结
The goal of this clinical trial is to learn about the effectiveness of repeated immunoadsorption intervention in patients with chronic fatigue syndrome (CFS) including patients with post-acute COVID-19 CFS (PACS-CFS).
The main questions it aims to answer are: (1) Does repeated immunoadsorption relieve fatigue and/or other symptoms associated with CFS and PACS-CFS? (2) Is repeated immunoadsorption safe and tolerable in this patient population? What are the side effects of repeated immunoadsorption, and how common are they?
Participants will be asked to participate for approx. 32 weeks (8 months). After screening, participants will receive assigned intervention of either five immunoadsorption treatments (with Ig adsorber) every other day over 10 days or matching sham treatments (without Ig adsorber), followed by a 6-month follow-up period with three ambulatory visits. Every participant will undergo trial outcome, safety, and monitoring assessments.
The results of this study will provide information on whether repeated immunoadsorption can alleviate symptoms associated with CFS and PACS-CFS, as well as insights into the pathophysiological processes in this condition, which in turn can help to develop new and effective therapies.
详细描述
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition with a varying prevalence of 0.3 - 3% and markedly restricts activity and function of patients. They experience severe fatigue even after minimal exercise or mental activity, together with a myriad of further symptoms such as cognitive impairment, poor sleep quality, muscle and joint pain, or headache. With the pandemic situation, ME/CFS related to post-acute COVID-19 syndrome (PACS) is becoming a raising issue. According to the WHO (in February 2022), there are more than 423 million confirmed cases of COVID-19 worldwide and a large proportion of patients discharged from hospital are suffering from persistent symptoms (Carfi et al., 2020; Davis et al., 2020).
The etiology and the mechanisms leading to the typical chronic course of ME/CFS or the pathophysiology of PACS are not fully understood. There is increasing evidence that a post-viral autoimmune reaction with the presence of autoantibodies targeting different neuronal tissues is involved in the pathogenesis.
This is a double-blinded, randomized, sham-controlled immunoadsorption (IA) study in patients with chronic fatigue syndrome (CFS) including patients with CFS related to post-acute COVID-19 syndrome (PACS-CFS). Primary endpoint of the study is clinical improvement 3 months after the completion of immunoadsorption (IA) quantified using the change from baseline of the Chalder Fatigue Scale (range 0-33). Patients are randomized 2:1 in order to provide therapy to as many patients as possible. During the screening period, all patients are tested for the presence of autoantibodies in blood and cerebrospinal fluid (CFS). A comprehensive characterization by CFS specific questionnaires, quality of life questionnaires (PROMIS), cognitive and neuropsychological testing (MOCA, CANTAB) is performed, and each patient is offered to receive an optional cranial MRI before and after immunoadsorption. Depending on the clinical phenotype, electromyography and pulmonary function testing will be done. We use established hand strength and finger tapping devices as well as an accelerometer to objectify clinical improvement. Patients are hospitalized for 9-12 days receiving IA 5 times every other day. Directly after completion of IA as well as at month 1, 3 and 6 there are followup visits.
The study will help to better understand disease mechanisms and thereby allow (hopefully biomarker associated) characterization of patients benefitting from such a costly but safe and often highly efficient therapy.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects of all genders ≥18 <65 years at time of informed consent
- •Diagnosed ME/CFS according to Canadian consensus criteria (CCC) 2003 including patients with PACS-CFS at screening with Bell Score ≥20 and ≤50
- •Detection of at least one kind of autoantibodies measured during screening (among others antineuronal-, ß2-adrenergic-receptor-, muscarine-receptorantibodies) in serum or CSF
排除标准
- •Comorbidity bearing risk that patient might not tolerate treatment as judged by investigator including among others:
- •malignant disease within the last 5 years
- •clinically meaningful laboratory abnormalities
- •moderate to severe renal insufficiency
- •cardiac insufficiency with an LVEF lower than 40%, uncontrolled cardiac arrhythmia, severe coronary heart disease
- •severe Hypercoagulability
- •Acute or severe psychiatric disease
- •Current indispensable medication with ACE inhibitors
- •Fatigue duration for ≥5 years
- •Presence of other conditions or differential diagnosis better explaining the symptoms of the patient than the suspected ME/CFS
- •Ongoing immunosuppressive therapy
- •Active/acute infectious diseases like TBC, HIV, CMV, EBV, HBV, HBC
结局指标
主要结局
Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale
时间窗: 3 months after completion of immunoadsorption or sham apheresis
The Chalder Fatigue Scale measures the extent and severity of tiredness and has been used in multiple randomized trials of behavioral interventions in patients with ME/CFS. Each of the 11 items is answered on a 4-point scale with an overall score ranging from 0 (asymptomatic) to 33 (maximum symptomology). Intra-patient change in physical and mental fatigue from baseline to month three will be documented as indexed by the Chalder Fatigue Scale.
次要结局
- Sustained improvement quantified by the Chalder Fatigue Scale(10 days, 1 month, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in severity of symptoms of chronic fatigue syndrome (CFS) as measured by the Fluge score(1 month, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in muscle fatigue measured by the repetitive hand grip strength test (HGS)(10 days, 3 months, and optional 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in symptoms of autonomic dysfunction as measured by the Composite Autonomic Symptom Score (COMPASS-31)(10 days, 3 months, and optional 6 months after completion of immunoadsorption or sham apheresis)
- Verification of safety and tolerability of immunoadsorption in this patient population(1 day, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in physical function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36)(1 month, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in functional disability as measured by the Bell disability scale(1 month, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in fatigue quantified by post exertional malaise (PEM) questionnaire(1 month, 3 months, and 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in quality of life (QoL) as measured by the PROMIS questionnaire(3 months and optional 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in symptoms of autonomic dysfunction by measuring blood pressure and heart rate regulation with the Schellong Test(10 days, 3 months, and optional 6 months after completion of immunoadsorption or sham apheresis)
- Improvement in neurocognitive functions as measured by the Montreal Cognitive Assessment (MoCA)(3 months and 6 months (only if requested by the investigator) after completion of immunoadsorption or sham apheresis)
- Improvement in neurocognitive functions as measured by the symbol digit modalities test (SDMT)(3 months and 6 months (only if requested by the investigator) after completion of immunoadsorption or sham apheresis)
- Changes in biomarkers of autoimmune activity(3 months after completion of immunoadsorption or sham apheresis)
- Changes in biomarkers of inflammation(3 months and 6 months after completion of immunoadsorption or sham apheresis)
研究者
Harald Pruess
Director of the Department of Experimental Neurology
Charite University, Berlin, Germany