A Placebo-Controlled, Double-Blind, Randomized Trial Phase I-II With Immunoadsorption in Autoimmune Long COVID
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Change in fatigue measured by the Fatigue Assessment Scale (FAS)
研究概览
简要总结
Some people continue to have serious symptoms long after COVID-19, such as extreme fatigue and feeling worse after activity. In some patients, this may happen because the immune system is attacking the body by mistake.
This study will test a treatment called immunoadsorption, which filters the blood to remove harmful antibodies. People with long COVID who have these antibodies will be randomly assigned to receive either the real treatment or a placebo. The main goal is to see whether fatigue improves after one month, and whether other symptoms and daily functioning improve over six months.
This research will help us find out if this treatment can benefit the group of long COVID patients with immune-related disease.
详细描述
Growing evidence indicates that autoantibodies may drive symptoms in a subset of people with long COVID, as demonstrated by symptom transfer to mice following administration of IgG from affected patients. This provides a strong rationale for targeted immunotherapy aimed at removing pathogenic antibodies. Immunoadsorption is a well-established method to reduce circulating IgG, but studies suggest that only a specific subgroup of patients benefits.
Using HuProt autoantibody microarray technology, we identified several autoantibodies uniquely present in long COVID patients compared with healthy controls. We subsequently developed and validated a disease-specific Luminex multiplex immunoassay to detect this autoimmune phenotype. This study will use these findings as a novel selection method of identifying long COVID patients with pathogenic IgG, thereby enriching the population most likely to benefit from immunoadsorption therapy.
This biomarker-guided personalized medicine approach could enhance treatment efficacy and advances long COVID therapeutic strategies. Additionally, the placebo-controlled and double blinded design will be needed to evaluate the true potential of autoantibodies adsorption therapy in long COVID. This study can add to our understanding on the role of autoantibodies in the pathogenesis of long COVID and could help in the development of precision-based immunotherapy for patients such as immunoadsorption.
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
- Double (Participant, Investigator)
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
- •Long COVID based on the WHO-criteria
- •PEM according to the DSQ-PEM
- •BELL's functionality score 20-70%
- •Good health prior to the long COVID diagnosis (WHO performance score 0)
排除标准
- •Medical history of clinically significant respiratory- or cardiovascular disease
- •Prior interventional cardiac procedure within 3 months prior to randomization
- •Active immunosuppresive treatment for systemic autoimmune disorders
- •Diabetes type 1
- •Solid organ malignancy in the last 5 years
- •Active psychiatric disorder currently under treatment by a psychiatrist
- •BMI > 35
- •Pre-existing fatigue
- •Poor performance score prior to the long COVID diagnosis (WHO performance >0)
- •Pregnancy or breastfeeding
研究组 & 干预措施
Placebo
Participants in the placebo group will receive six sessions of sham treament, each lasting 2.5 hours over two weeks. The procedure will be performed without an adsorption column, allowing the blood to circulate through the extracorporeal circuit and be returned to the patient without removal of immunoglobulins or other plasma components.
干预措施: Sham Comparator (Device)
Immunoadsorption
Participants in the intervention group will receive six sessions of immunoadsorption, each lasting 2.5 hours over two weeks. Immunoadsorption will be performed using tryptophan columns, which bind the Fc region of IgG via hydrophobic and aromatic interactions.
干预措施: Immunoadsorption (Device)
结局指标
主要结局
Change in fatigue measured by the Fatigue Assessment Scale (FAS)
时间窗: At baseline and 28 days after start treatment
Score range 10-50 (10 items, Likert scale 1-5). Higher scores indicate more severe fatigue (worse). The difference in scores from baseline will be measured (MCID of 4 points) as the primary outcome.
次要结局
- Change in health related quality of life using the 36-Item Short Form Health Survey (SF-36)(At baseline and days 28, 60, 90, and 180)
- Change in cognitive functioning using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Cognitive Function Short Form 8a (PROMIS Cognitive Function Short Form 8a)(At baseline and days 28, 60, 90, and 180)
- Change in autonomic symptoms using the Composite Autonomic Symptom Score-31 (COMPASS-31)(At baseline and days 28, 60, 90, and 180)
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) related to the intervention(From first study intervention through day 180)
- Repeated Handgrip Strength(At baseline and days 28, 60, 90, and 180)
- Orthostatic intolerance using the NASA lean test(At baseline and days 28 and 180)
- Efficacy treatment by measuring immunoglobuline titers(At baseline (prior to treatment initiation), during treatment, and at days 28 and 180 after treatment initiation.)
- Autoantibody score using an in-house Luminex assay(At screening and on days 28, 60, 90, and 180)
研究者
W. J. Wiersinga, MD
Prof. Dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)