Immunoadsorption Versus Immunoglobulins for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Study Overview
=================
Brief Summary
-----------------
This is a randomized controlled study evaluating safety and efficacy of repeated immunoadsorption versus immunoglobulins in steroid-refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

Official Title
-----------------
Immunoadsorption Versus Immunoglobulins for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Conditions
-----------------
CIDP

Intervention / Treatment
-----------------
* Device: Immunoadsorption
* Biological: Immunoglobulins


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of possible, probable, or definite CIDP (typical or atypical) according to European Federation of Neurological Societies (EFNS) guidelines Disease duration of 3 years or less Age 18 years or above Previous treatment with methyl-prednisolone and insufficient therapeutic response as judged by the treating physician, or contraindications against methyl-prednisolone, or clinically significant side effects under methyl-prednisolone therapy as judged by the treating physician Exclusion Criteria: Clinical or laboratory evidence of manifest systemic infection, i.e., C-reactive protein (CRP) above 20 mg/l, or evidence of nitrite-positive urinary tract infection Intake of angiotensin converting enzyme inhibitor within 1 week before first treatment immunoglobulin A deficiency Other contraindications against immunoadsorption or intravenous immunoglobulins

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoadsorption<br>3 cycles of immunoadsorption in week 1, 7, and 13 after randomization. One cycle consists of 5 sessions on 5 consecutive days with processing of the 2-fold plasma volume on the first day and the 2.5-fold plasma volume on consecutive days, using regenerative adsorbers (Therasorb, Miltenyi Biotec, Bergisch Gladbach) | Device: Immunoadsorption<br>* see arm/group description<br>|
| Active Comparator: Immunoglobulins<br>5 cycles of intravenous immunoglobulins in week 1, 4, 7, 10, and 13 after randomization. The first cycle consists of 5 intravenous applications of immunoglobulins on 5 consecutive days in a dosage of 0.4 g per kg body weight per day. Subsequent cycles consist of 2 intravenous applications of immunoglobulins on 2 consecutive days in a dosage of 0.5 g per kg body weight per day. | Biological: Immunoglobulins<br>* see arm/group description<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CIDP Score | The CIDP Score is a combined score of Inflammatory Cause and Treatment (INCAT) Disability Score, Oxford Muscle Strength Score, and Vibration Score, with each subscore equally weighted. | 15 weeks | 
| Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Standard clinical score for CIDP, quantifying disability. | 15 weeks | 
| Oxford Muscle Strength Score (Medical Research Council, MRC) | Standard clinical score for evaluation of muscle strength / paresis. Muscle strength is evaluated on a scale between 0/5 (no movement) and 5/5 (full strength) at 8 pre-defined muscles (one proximal and one distal muscle at each extremity). | 15 weeks | 
| Vibration Score | Standard clinical score for evaluation of pallesthesia, using a 256 Hz tuning fork. The individual perception threshold for vibration sensations on a scale between 0/8 (no perception) and 8/8 (normal perception) will be determined at 4 predefined spots (processus styloideus radii and malleolus lateralis on each side). | 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CIDP Score | The CIDP Score is a combined score of Inflammatory Cause and Treatment (INCAT) Disability Score, Oxford Muscle Strength Score, and Vibration Score, with each subscore equally weighted. | 1, 7, and 13 weeks | 
| Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Standard clinical score for CIDP, quantifying disability. | 1, 7, and 13 weeks | 
| Oxford Muscle Strength Score (Medical Research Council, MRC) | Standard clinical score for evaluation of muscle strength / paresis. Muscle strength is evaluated on a scale between 0/5 (no movement) and 5/5 (full strength) at 8 pre-defined muscles (one proximal and one distal muscle at each extremity). | 16 weeks | 
| Vibration Score | Standard clinical score for evaluation of pallesthesia, using a 256 Hz tuning fork. The individual perception threshold for vibration sensations on a scale between 0/8 (no perception) and 8/8 (normal perception) will be determined at 4 predefined spots (processus styloideus radii and malleolus lateralis on each side). | 16 weeks | 
| Pain | Quantifying pain on a Visual Analog Scale between 0 (no pain) and 10 (maximum pain). | 1, 7, 13, and 15 weeks | 
| N20 Latency | N20 latency of Nervus medianus (both sides) in somatosensory evoked potentials (SEPs). | 15 weeks | 
| P40 Latency | P40 latency of Nervus tibialis (both sides) in somatosensory evoked potentials (SEPs). | 15 weeks | 
| Nerve Conduction Velocity | Nerve conduction velocities of clinically affected nerves as measured by electroneurography (ENG). | 15 weeks | 
| Euro Quality of Life 5 Dimension 5 Levels (EQ-5D-5L) | Quality of Life Scale | 1, 7, 13, and 15 weeks | 
| Immunoglobulin A | Immunoglobulin A serum levels | 1, 7, 13, and 15 weeks | 
| Immunoglobulin G | Immunoglobulin G serum levels | 1, 7, 13, and 15 weeks | 
| Immunoglobulin M | Immunoglobulin M serum levels | 1, 7, 13, and 15 weeks | 
| Interleukin-1 | Interleukin-1 serum levels | 1, 7, 13, and 15 weeks | 
| Interleukin-6 | Interleukin-6 serum levels | 1, 7, 13, and 15 weeks | 
| Anti-contactin-1 | Anti-contactin-1 serum levels | 1, 7, 13, and 15 weeks | 
| Anti-neurofascin155 | Anti-neurofascin155 serum levels | 1, 7, 13, and 15 weeks | 
| Anti-contactin-associated-protein1 | Anti-contactin-associated-protein1 serum levels | 1, 7, 13, and 15 weeks | 
| Anti-neurofascin186 | Anti-neurofascin186 serum levels | 1, 7, 13, and 15 weeks | 
| Anti-neurofascin140 | Anti-neurofascin140 serum levels | 1, 7, 13, and 15 weeks | 
| Neurofilament Light Chain (NfL) | Neurofilament light chain (NfL) serum levels | 1, 7, 13, and 15 weeks | 
| Therapeutic Response | Share of patients with at least 10% improvement in CIDP score compared to baseline. | 15 weeks |