Observational Study on Immunoadsorption (IA) in Patients With Autoantibody-Positive Post-Infectious ME/CFS

Официальное название

Observational Study on Immunoadsorption (IA) in Patients With Autoantibody-Positive Post-Infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Обзор

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe, often infection-triggered disease characterized by debilitating fatigue and post-exertional malaise lasting over 14 hours, along with pain, cognitive impairment, autonomic dysfunction, and sleep disturbances. Around 10% of patients after mild or moderate COVID-19 develop Post-COVID Syndrome (PCS), and some meet ME/CFS criteria after six months. No causal treatment exists for ME/CFS or PCS; current approaches are symptomatic and rehabilitative. Given the high and increasing number of affected patients, there is an urgent need for evidence-based, standardized therapies. Immunoadsorption (IA) is an established treatment for several autoimmune diseases. The first study demonstrating successful IA use in PCS-associated ME/CFS was published by our group in 2024. Earlier proof-of-concept studies (2018, 2020) in infection-related ME/CFS also showed symptomatic improvement in most patients. Hypothesis: Antibody depletion through IA improves symptoms in the majority of patients with autoantibody-positive ME/CFS and is associated with altered memory B-cell profiles before treatment. Objective: To observe and document symptom progression in 50 ME/CFS or PCS patients undergoing IA, and to examine whether changes in memory B-cells before treatment are linked to therapeutic response. The study is conducted as a non-interventional observational study. IA using the TheraSorb® column (Miltenyi) is performed within its approved clinical application.

Подробное описание

Patients presenting to our outpatient clinic who meet the Canadian Consensus Criteria (CCC) for ME/CFS and show detectable autoantibodies are offered IA as part of routine care. Those undergoing IA are invited to participate in this observational study. Post-COVID patients fulfilling the CCC are also eligible for IA and study inclusion.

IA is performed independently of the study at the Diamedikum Potsdam. The standard clinical schedule includes five outpatient sessions on days 1, 2, 4, 6, and 8. This procedure follows routine clinical practice and is not influenced by study participation.

At study inclusion, all patients undergo baseline assessments including routine laboratory tests, immunoglobulins, autoantibodies, and biomarkers, with a total of 50 ml of blood collected. Additional diagnostic workup is performed as clinically indicated. The diagnosis of ME/CFS is confirmed using the CCC.

Health status and symptom severity are documented using validated questionnaires: SF-36 (Physical Function subscale), work ability (past 12 months), weighted CCC symptom score, Chalder Fatigue Questionnaire, and Bell Disability Scale. These are completed monthly for 12 months after treatment. To reduce participant burden, questionnaires are mailed to patients for home completion.

Further clinical and laboratory assessments are conducted before IA and at 2- and 6-months post-treatment: i) Handgrip strength, ii) NASA Lean Test, and iii) Blood sampling.

The total study duration per participant is 12 months after IA.

This is a non-interventional observational study following patients with ME/CFS or PCS undergoing IA using the TheraSorb® Immunoadsorption system (Miltenyi) within its approved indication.

Evidence on the effectiveness of IA for ME/CFS including PCS exists only from clinical studies. This observational study aims to provide data to support a future randomized controlled trial (RCT).

Вмешательства

• Устройство IA with TheraSorb ® column (Miltenyi)
  IA cycle is 5 days (1-2-4-6-8); the procedure follows routine clinical practice.

Первичные конечные точки

• Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) [Срок оценки: 8 weeks after first IA]

Вторичные конечные точки (8)

• Improvement in ability to work in daily hours [Срок оценки: before first IA; 3 and 6 months after last IA]
• Improvement in hand grip strength [Срок оценки: 8 weeks after first IA]
• Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale [Срок оценки: 8 weeks after first IA; 3 and 6 months after last IA]
• Improvement in symptoms of ME/CFS as measured by Canadian Consensus Criteria (CCC) Symptom Score [Срок оценки: 8 weeks after first IA; 3 and 6 months after last IA]
• Improvement in symptoms of autonomic dysfunction as measured by the Composite Autonomic Symptom Score (COMPASS-31) [Срок оценки: 8 weeks after first IA; 3 and 6 months after last IA]
• Decrease in ß2R autoantibodies and soluble biomarkers of disease [Срок оценки: 8 weeks after first IA]
• Correlation of treatment response with memory B-cells [Срок оценки: 8 weeks after first IA]
• Verification of tolerability [Срок оценки: 8 weeks after last IA]

Критерии участия

Критерии включения

• Patients aged 18-65 years who are able to give informed consent and have: i) ME/CFS diagnosed according to the CCC, with exertion intolerance and symptom worsening (post exertional malaise = PEM) lasting at least 14 hours and ii) Significant functional impairment with a Bell Disability Score < 60
• Presence of autoantibodies (adrenergic or antineuronal antibodies)
• Undergoing IA with the TheraSorb® column over 5 days
• Written informed consent provided by the patient
• Health insurance coverage

Критерии исключения

• Lack of willingness to store pseudonymized disease data as part of the study
• Pregnancy
• Presence of other conditions that prevent a definite ME/CFS diagnosis (e.g., heart failure, lung disease, severe depression, cancer)
• Acute infection (COVID, HIV, hepatitis)
• Severe fatigue disease with bedriddenness (Bell Disability Score < 30)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 1 центр

• Charité - Universitätsmedizin Berlin — Berlin

Публикации

• Tolle M, Freitag H, Antelmann M, Hartwig J, Schuchardt M, van der Giet M, Eckardt KU, Grabowski P, Scheibenbogen C. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption. J Clin Med. 2020 Jul 30;9(8):2443. doi: 10.3390/jcm9082443. PMID 32751659
• Scheibenbogen C, Loebel M, Freitag H, Krueger A, Bauer S, Antelmann M, Doehner W, Scherbakov N, Heidecke H, Reinke P, Volk HD, Grabowski P. Immunoadsorption to remove ss2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. PLoS One. 2018 Mar 15;13(3):e0193672. doi: 10.1371/journal.pone.0193672. eCollection 2018. PMID 29543914
• Stein E, Heindrich C, Wittke K, Kedor C, Rust R, Freitag H, Sotzny F, Kruger A, Tolle M, Grabowski P, Scheibenbogen C, Kim L. Efficacy of repeated immunoadsorption in patients with post-COVID myalgic encephalomyelitis/chronic fatigue syndrome and elevated beta2-adrenergic receptor autoantibodies: a prospective cohort study. Lancet Reg Health Eur. 2024 Dec 12;49:101161. doi: 10.1016/j.lanepe.2024.1 PMID 39759581
• Sotzny F, Filgueiras IS, Kedor C, Freitag H, Wittke K, Bauer S, Sepulveda N, Mathias da Fonseca DL, Baiocchi GC, Marques AHC, Kim M, Lange T, Placa DR, Luebber F, Paulus FM, De Vito R, Jurisica I, Schulze-Forster K, Paul F, Bellmann-Strobl J, Rust R, Hoppmann U, Shoenfeld Y, Riemekasten G, Heidecke H, Cabral-Marques O, Scheibenbogen C. Dysregulated autoantibodies targeting vaso- and immunoregulato PMID 36238301
• Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat PMID 36042189
• Scheibenbogen C, Kedor C, Behrends U. ME/CFS, Der niedergelassene Arzt, 12/2020

Идентификаторы

NCT: NCT07529197 · IMPACT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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