Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome

Study Overview
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Brief Summary
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The complex clinical symptoms of post COVID syndrome, especially chronic fatigue, pose a major challenge to patients and to the health care system and are frequently refractory to therapeutic intervention. There is increasing evidence that a dysregulated post-viral immune response may be involved in the pathogenesis of post COVID syndrome. In uncontrolled case studies, an improvement of fatigue symptoms after removing autoantibodies has been reported in post COVID patients. However, there is a lack of prospective, sham controlled studies. We initiate an interventional, randomised, sham treatment-controlled prospective study, the EXTINCT post COVID study, which aims to scientifically test the therapeutic efficacy of an extracorporeal apheresis procedure (immunoadsorption) for the treatment of a well characterized cohort of patients with post COVID syndrome, while at the same time providing basic research evidence for an understanding of the pathogenesis of post COVID syndrome. Thereby, we expect to obtain important insights into the diagnosis, treatment and pathophysiology of post-COVID syndrome.

Official Title
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Extracorporal Apheresis Hannover Medical School Study in Post COVID-19 Patients

Conditions
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Fatigue, Post-Acute COVID-19 Syndrome

Intervention / Treatment
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* Procedure: Immunoadsorption vs. sham immunoadsorption


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Chronic Fatigue Syndrome (CFS) according to Canadian Consensus Criteria (at two time points > 4 weeks apart) with a duration of > 6 months with new onset < 12 weeks after PCR test confirmed SARS-CoV2-infection Chalder Fatigue Scale >/= 4 binary scale (at two time points > 4 weeks apart) Post exertional malaise >/= 14 h (at two time points > 4 weeks apart) Bell Scale 20-50 (at two time points > 4 weeks apart) Willing to comply with all aspects of the protocol, including blood draws, magnetic resonance imaging and ophthalmological evaluation Patient is able to understand and fully participate in the activities of the study and consent in accordance with guidelines Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. Female patients must not be pregnant, planning to become pregnant, or be actively breastfeeding through the entire period. Exclusion citeria: Chronic fatigue due to other medical or psychological condition Preexisting chronic fatigue prior to COVID infection Oxygen requirement or ventilation during acute phase of COVID Positive SARS-CoV-2-PCR test at the beginning of the study Comorbidity bearing risk that patient might not tolerate treatment as judged by investigator including among others: malignant disease within the last 5 years, moderate to severe renal impairment (eGFR <60 ml/min), cardiac insufficiency (LVEF <40%), severe coronary heart disease, severe hypercoagulability Acute or severe psychiatric disease Active/acute infectious diseases like CMV, EBV, HBV, HCV, HIV, TBC Patients who in the investigator's opinion might not be suitable for study (difficult peripheral venous access, not able to complete questionnaires e.g. due to language problems) Taking immunosuppressive medication >3 weeks within 12 months before study inclusion Any apheresis therapy before study inclusion Contraindications for magnetic resonance imaging Patients revealing abnormal brain structures visible in MR images Patients with pre-existing ophthalmological condition or diabetes mellitus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded, randomized, sham-controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoadsorption<br>5 immunoadsorption treatments | Procedure: Immunoadsorption vs. sham immunoadsorption<br>* 5 treatments within 14 days<br>* Other names: Apheresis;|
| Sham Comparator: Sham immunoadsorption<br>5 sham immunoadsorption treatments | Procedure: Immunoadsorption vs. sham immunoadsorption<br>* 5 treatments within 14 days<br>* Other names: Apheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chalder Fatigue Scale | Time course of fatigue symptoms as determined based on Chalder Fatigue Scale (ranging from 0 to 33), higher values indicating a higher burden of fatigue symptoms | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Function | Assessment of cognitive function measured by Montreal Cognitive Assessment (Scale 0-30), lower values indicating cognitive impairment | 12 weeks | 
| Post exertional malaise symptoms | Assessment of frequency and severity of post exertional malaise symptoms (frequency: 0-20, severity: 0-20, duration), higher values indicating a higher burden of post exertional malaise symptoms | 12 weeks | 
| Measure of health status | Evaluation of health status by Short Form Health Survey (SF-36) | 12 weeks | 
| Depression and Anxiety | Symptoms of depression and anxiety measured by Hospital Anxiety and Depression Scale (HADS) | 12 weeks | 
| Autonomic dysfunction | Symptoms of autonomic dysfunction assessed by Composite Autonomic Symptom Score (COMPASS 31), generating a weighted score from 0 to 100, with higher scores representing higher symptom burden | 12 weeks | 
| 6-min. walk test | Walking distance, oxygen saturation, heart rate and dyspnea assessed during 6-min. walk test | 12 weeks | 
| Hand grip strength | Hand grip strength measured via digital hand dynamometer | 12 weeks | 
| Optical coherence tomography angiography | Assessment of retinal microcirculation | 12 weeks | 
| Cranial magnetic resonance imaging and spectroscopy | Cranial magnetic resonance imaging and assessment of region-dependent metabolic distributions | 12 weeks | 
| Symptoms related to chronic fatigue before and after immunoadsorption | Change of symptoms as measured by Fluge score, using a scale ranging from 1 to 10 (higher values representing higher symptom load) assessing 32 fatigue related symptoms and their intra-patient change from baseline to follow-up | 12 weeks | 
| Neurocognitive function | Attentional deficits as assessed by Test of Attentional Performance | 12 weeks |