Immunoadsorption in Patients With Chronic Fatigue Syndrome Including Patients With Post-COVID-19 CFS

Charité University Medicine Berlin

Status: Completed

Conditions: Post-COVID ME/CFS; ME/CFS

Treatments: Device: Immunoadsorption

Study type: Interventional

Funder types: Other

Identifiers

NCT05710770

IA-PACS-CFS

01EP2201 (Other Grant/Funding Number)

Details and patient eligibility

About

The goal of this clinical trial is to learn about the effectiveness of repeated immunoadsorption intervention in patients with chronic fatigue syndrome (CFS) including patients with post-acute COVID-19 CFS (PACS-CFS).

The main questions it aims to answer are: (1) Does repeated immunoadsorption relieve fatigue and/or other symptoms associated with CFS and PACS-CFS? (2) Is repeated immunoadsorption safe and tolerable in this patient population? What are the side effects of repeated immunoadsorption, and how common are they?

Participants will be asked to participate for approx. 32 weeks (8 months). After screening, participants will receive assigned intervention of either five immunoadsorption treatments (with Ig adsorber) every other day over 10 days or matching sham treatments (without Ig adsorber), followed by a 6-month follow-up period with three ambulatory visits. Every participant will undergo trial outcome, safety, and monitoring assessments.

The results of this study will provide information on whether repeated immunoadsorption can alleviate symptoms associated with CFS and PACS-CFS, as well as insights into the pathophysiological processes in this condition, which in turn can help to develop new and effective therapies.

Full description

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition with a varying prevalence of 0.3 - 3% and markedly restricts activity and function of patients. They experience severe fatigue even after minimal exercise or mental activity, together with a myriad of further symptoms such as cognitive impairment, poor sleep quality, muscle and joint pain, or headache. With the pandemic situation, ME/CFS related to post-acute COVID-19 syndrome (PACS) is becoming a raising issue. According to the WHO (in February 2022), there are more than 423 million confirmed cases of COVID-19 worldwide and a large proportion of patients discharged from hospital are suffering from persistent symptoms (Carfi et al., 2020; Davis et al., 2020).

The etiology and the mechanisms leading to the typical chronic course of ME/CFS or the pathophysiology of PACS are not fully understood. There is increasing evidence that a post-viral autoimmune reaction with the presence of autoantibodies targeting different neuronal tissues is involved in the pathogenesis.

This is a double-blinded, randomized, sham-controlled immunoadsorption (IA) study in patients with chronic fatigue syndrome (CFS) including patients with CFS related to post-acute COVID-19 syndrome (PACS-CFS). Primary endpoint of the study is clinical improvement 3 months after the completion of immunoadsorption (IA) quantified using the change from baseline of the Chalder Fatigue Scale (range 0-33). Patients are randomized 2:1 in order to provide therapy to as many patients as possible. During the screening period, all patients are tested for the presence of autoantibodies in blood and cerebrospinal fluid (CFS). A comprehensive characterization by CFS specific questionnaires, quality of life questionnaires (PROMIS), cognitive and neuropsychological testing (MOCA, CANTAB) is performed, and each patient is offered to receive an optional cranial MRI before and after immunoadsorption. Depending on the clinical phenotype, electromyography and pulmonary function testing will be done. We use established hand strength and finger tapping devices as well as an accelerometer to objectify clinical improvement. Patients are hospitalized for 9-12 days receiving IA 5 times every other day. Directly after completion of IA as well as at month 1, 3 and 6 there are followup visits.

The study will help to better understand disease mechanisms and thereby allow (hopefully biomarker associated) characterization of patients benefitting from such a costly but safe and often highly efficient therapy.

Enrollment: 66 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects of all genders ≥18 <65 years at time of informed consent
• Diagnosed ME/CFS according to Canadian consensus criteria (CCC) 2003 including patients with PACS-CFS at screening with Bell Score ≥20 and ≤50
• Detection of at least one kind of autoantibodies measured during screening (among others antineuronal-, ß2-adrenergic-receptor-, muscarine-receptorantibodies) in serum or CSF

Exclusion criteria

• Comorbidity bearing risk that patient might not tolerate treatment as judged by investigator including among others:

  • malignant disease within the last 5 years
  • clinically meaningful laboratory abnormalities
  • moderate to severe renal insufficiency
  • cardiac insufficiency with an LVEF lower than 40%, uncontrolled cardiac arrhythmia, severe coronary heart disease
  • severe Hypercoagulability

• Acute or severe psychiatric disease

• Current indispensable medication with ACE inhibitors

• Fatigue duration for ≥5 years

• Presence of other conditions or differential diagnosis better explaining the symptoms of the patient than the suspected ME/CFS

• Ongoing immunosuppressive therapy

• Active/acute infectious diseases like TBC, HIV, CMV, EBV, HBV, HBC

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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66 participants in 2 patient groups

Immunoadsorption

Active Comparator group

Description:

Immunoadsorption will be conducted with the TheraSorb LIFE 21 apheresis system in combination with the TheraSorb-Ig omni 5 adsorber over a period of 9-12 days: each participant will receive five immunoadsorption cycles treating 2.0 - 2.5 patient's plasma volumes every other day. Initial pilot studies have demonstrated this dose finding to be effective and well tolerated (Scheibenbogen et al., 2018; Tolle et al., 2020). The immunoapheresis material will be provided by the Miltenyi company at the beginning of the study. Concerning the high effectiveness of immunoadsorption therapy in patients with other neuroimmunological diseases and the invasiveness of a sham-apheresis, a 2:1 randomization was chosen in order to ensure that more patients will receive a verum IA treatment.

Treatment:

Device: Immunoadsorption

Sham-apheresis

Sham Comparator group

Description:

To have identical conditions to the immunoadsorption, sham apheresis will also be conducted with the TheraSorb LIFE 21 apheresis system over a period of 9-12 days: each participant will receive five sham cycles. For the sham apheresis, a TheraSorb LIFE 21 unit with blocked Ig adsorbers and without regeneration of the adsorbers during the treatment will be used, ensuring that the patient and the investigator are blinded. The study nurses applying the treatment (a specific person only in charge of the patient during the treatment) cannot be blinded.

Treatment:

Device: Immunoadsorption