Immunoadsorption Versus High-dose Intravenous Corticosteroids in Relapsing Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
Treatment of acute relapsing multiple sclerosis (MS) has remained largely unaltered within past years. However, evidence defining the exact role of apheresis treatment in the therapeutic sequence is still incomplete. INCIDENT-MS evaluates the mechanism of action of immunoadsorption compared to escalated methyl prednisolone treatment in steroid-refractory MS relapses and thereby will help to identify predictive markers for optimal treatment choice and will generate further insights into the pathophysiology of MS relapses.

Official Title
-----------------
Immunoadsorption Versus High-dose Intravenous Corticosteroids in Relapsing Multiple Sclerosis - Assessment of Mechanism of Action

Conditions
-----------------
Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
-----------------
* Drug: Methyl Prednisolonate
* Procedure: Immunoadsorption


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form Diagnosis of relapsing-remitting multiple sclerosis according to 2017 revised McDonald-criteria Incomplete remission of relapse symptoms following initiation treatment with 1000mg/d intravenous methyl prednisolone Absence of fever or clinically apparent signs of infection Exclusion Criteria: Baseline EDSS score >6.5 points Previous administration of less than 3x1000mg or more than 5x1000mg IVMPS for initiation treatment Known pregnancy or rejection to perform a pregnancy test (female patients only) Immunosuppressive treatment for conditions other than multiple sclerosis Ongoing neoplastic disorder or past neoplastic disorder within previous five years Known or newly diagnosed HIV-, HBV- or HCV-infection Regular intake of ACE inhibitor drugs Known bleeding disorders (including laboratory abnormalities such as: (I) platelet count<50.000/µL; (II) international normalized ratio>1.5, (III) activated prothrombin time>50s) or intake of oral anticoagulant drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intravenous methyl prednisolone<br>Patients receiving an additional course of intravenous methyl prednisolone for treatment of a steroid-refractory MS relapse | Drug: Methyl Prednisolonate<br>* 2000mg intravenous methyl prednisolone per day for five consecutive days<br>|
| Immunoadsorption<br>Patients receiving 6 courses of immunadsorption treatment for treatment of a steroid-refractory MS relapse | Procedure: Immunoadsorption<br>* 6 courses of tryptophane-based immunoadsorption within up to 12 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded disability status scale (EDSS) | Improvement of disability compared to peak relapse EDSS following escalation treatment compared to peark relapse values | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual-evoked potentials (VEP; P100-latency) | Evolution of VEP P100-latency compared to peak relapse values | 2 weeks; 6 to 8 weeks | 
| somatosensory-evoked potentials (SEP; Medianus and Tibialis; N20-, P40-latency) | Evolution of SEP N20-/P40-latency compared to peak relapse values | 2 weeks; 6 to 8 weeks | 
| best-corrected visual acuity (bcVA) | Evolution of bcVA compared to peak relapse values | 2 weeks; 6 to 8 weeks | 
| Expanded disability status scale (EDSS) | Confirmation of improvement of disability compared to primary endpoint | 6 to 8 weeks | 
| Multiple scleroris functional compositie (MSFC) | Development of MSFC z-score compared to peak relapse values | 2 weeks, 6 to 8 weeks | 
| Short form-36 questionaire (SF-36) | Development of quality-of-life compared to peak relapse values | 6 to 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immunoadsorption, intravenous methyl prednisolone