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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Post-Acute COVID-19 Syndrome
• Intervention / Treatment: Procedure: Immunoadsorption vs. sham immunoadsorption

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr. Goedecke, MD; Phone Number: 3000 0049-511-532-0; Email: studienzentrum@mh-hannover.de
• Study Contact Backup: Name: Prof. Schmidt, MD; Phone Number: 3000 0049-511-532-0; Email: studienzentrum@mh-hannover.de

Study Locations

• Germany
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Recruiting
      • Hannover Medical School
      • Contact: Hannover Medical School; Phone Number: 3000 0049-511-532-0; Email: studienzentrum@mh-hannover.de

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-75 years
2. 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
3. Chalder Fatigue Scale >/= 4 binary scale (at two time points > 4 weeks apart)
4. Post exertional malaise >/= 14 h (at two time points > 4 weeks apart)
5. Bell Scale 20-50 (at two time points > 4 weeks apart)
6. Willing to comply with all aspects of the protocol, including blood draws, magnetic resonance imaging and ophthalmological evaluation
7. Patient is able to understand and fully participate in the activities of the study and consent in accordance with guidelines
8. 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:

1. Chronic fatigue due to other medical or psychological condition
2. Preexisting chronic fatigue prior to COVID infection
3. Oxygen requirement or ventilation during acute phase of COVID
4. Positive SARS-CoV-2-PCR test at the beginning of the study
5. 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
6. Acute or severe psychiatric disease
7. Active/acute infectious diseases like CMV, EBV, HBV, HCV, HIV, TBC
8. 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)
9. Taking immunosuppressive medication >3 weeks within 12 months before study inclusion
10. Any apheresis therapy before study inclusion
11. Contraindications for magnetic resonance imaging
12. Patients revealing abnormal brain structures visible in MR images
13. Patients with pre-existing ophthalmological condition or diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoadsorption; 5 immunoadsorption treatments	Procedure: Immunoadsorption vs. sham immunoadsorption; 5 treatments within 14 days; Other Names: Apheresis
Sham Comparator: Sham immunoadsorption; 5 sham immunoadsorption treatments	Procedure: Immunoadsorption vs. sham immunoadsorption; 5 treatments within 14 days; Other Names: Apheresis

What is the study measuring?

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
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
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
Cranial magnetic resonance imaging and spectroscopy	Cranial magnetic resonance imaging and assessment of region-dependent metabolic distributions	12 weeks
Neurocognitive function	Attentional deficits as assessed by Test of Attentional Performance	12 weeks
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
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
Optical coherence tomography angiography	Assessment of retinal microcirculation	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of immunoadsorption treatment	Number of treatment emergent adverse events, serious adverse events and discontinuation due to treatment emergent adverse events	12 weeks

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Dr. Goedecke, MD, Hannover Medical School, Department of Nephrology and Hypertension

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Fatigue; Immunoadsorption; Post COVID syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Disease; Chronic Disease; Post-Infectious Disorders; COVID-19; Syndrome; Fatigue; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: EXTINCT post COVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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