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

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

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.

Study Overview

• Status: Recruiting
• Conditions: ME/CFS Following COVID-19; Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
• Intervention / Treatment: Device: IA with TheraSorb ® column (Miltenyi)

Detailed Description

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).

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Elisa A Stein, Dr.; Phone Number: +49 450 624354; Email: elisa.stein@charite.de

Study Locations

• Germany
  • State of Berlin
    • Berlin, State of Berlin, Germany, 10117
      • Recruiting
      • Charite - Universitatsmedizin Berlin
      • Contact: Carmen Scheibenbogen, Prof. Dr.; Phone Number: +49 30 450 524103; Email: carmen.scheibenbogen@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to our outpatient clinic who meet the 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 criteria are also eligible for IA and study inclusion.

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36)	The SF-36 is an established and widely used health-related quality of life measure. The PF domain asks patients to report limitations on ten mobility activities, such as walking specified distances, carrying groceries, and bathing or dressing. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, i.e., severe disability) to 100 (no health restrictions). An intra-patient change of 10 points in SF-36-PF from baseline to week four is considered clinically meaningful.	8 weeks after first IA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in ability to work in daily hours	Number of patients with an intra-patient change in his/her/their ability to work in daily hours from 6 months before first IA to 12 months after last IA.	before first IA; 3 and 6 months after last IA
Improvement in hand grip strength	Intra-patient change in hand grip strength from baseline to follow-up points assessed using the Handgrip-Muscle-Fatigue Test.	8 weeks after first IA
Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale	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 follow-up points will be documented as indexed by the Chalder Fatigue Scale.	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	The CCC Symptom Score quantifies ME/CFS symptoms. Its score ranges from 1 (no symptoms) to 10 (extreme symptoms). Intra-patient change in ME/CFS symptoms from baseline to follow-up points will be documented as indexed by the CCC Symptom Score.	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)	The COMPASS-31 is a refined, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, applies a much-simplified scoring algorithm, and is suitable for widespread use in autonomic research and practice. It evaluates six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains. The score ranges from 0 (no symptoms) to 100 (strong autonomic dysfunction). Intra-patient change in autonomic dysfunction from baseline to follow-up points will be documented as indexed by the COMPASS-31.	8 weeks after first IA; 3 and 6 months after last IA
Decrease in ß2R autoantibodies and soluble biomarkers of disease	Intra-patient change in ß2R autoantibodies and soluble biomarkers of disease from baseline to follow-up points assessed.	8 weeks after first IA
Correlation of treatment response with memory B-cells	Associations of intra-patient change in symptoms and profile or levels of memory B-cells from baseline to follow-up points.	8 weeks after first IA
Verification of tolerability	Number of patients tolerating the IA treatment.	8 weeks after last IA

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: German Federal Ministry of Research, Technology, and Space (BMFTR); Weidenhammer-Zöbele Foundation
• Investigators: Principal Investigator: Carmen Scheibenbogen, Prof. Dr., Institute of Medical Immunology, Charité - Universitätsmedizin Berlin,

Publications and helpful links

General Publications

• Tölle 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. 9(8):2443, 2020
• 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. e0193672; 2018
• Stein E, Heindrich C, Wittke K, Kedor C, Rust R, Freitag H, Sotzny F, Krüger A, Tölle M, Grabowski P, Scheibenbogen C, Kim L. Efficacy of repeated immunoadsorption in patients with post-COVID myalgic encephalomyelitis/chronic fatigue syndrome and elevated β2-adrenergic receptor autoantibodies: a prospective cohort study. Lancet Reg Health Eur. 2024 Dec 12;49:101161.
• Sotzny F, Filgueiras IS, Kedor C, Freitag H, Wittke K, Bauer S, et al. Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity. Front Immunol. 2022;13:981532.
• 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 Commun. 2022;13:5104.
• Scheibenbogen C, Kedor C, Behrends U. ME/CFS, Der niedergelassene Arzt, 12/2020

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Post-COVID Syndrome (PCS); Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); Immunoadsorption (IA); SF-36 Physical Function (PF)
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Encephalomyelitis; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathological Conditions, Signs and Symptoms; Fatigue Syndrome, Chronic; Therapeutics; Surgical Procedures, Operative; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Plasmapheresis
• Other Study ID Numbers: IMPACT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No