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

Primary Purpose

CIDP

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Immunoadsorption
Immunoglobulins
Sponsored by
University of Ulm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CIDP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Neurology, University of UlmRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Immunoadsorption

Immunoglobulins

Arm Description

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)

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.

Outcomes

Primary Outcome Measures

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.
Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Standard clinical score for CIDP, quantifying disability.
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).
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).

Secondary Outcome Measures

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.
Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Standard clinical score for CIDP, quantifying disability.
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).
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).
Pain
Quantifying pain on a Visual Analog Scale between 0 (no pain) and 10 (maximum pain).
N20 Latency
N20 latency of Nervus medianus (both sides) in somatosensory evoked potentials (SEPs).
P40 Latency
P40 latency of Nervus tibialis (both sides) in somatosensory evoked potentials (SEPs).
Nerve Conduction Velocity
Nerve conduction velocities of clinically affected nerves as measured by electroneurography (ENG).
Euro Quality of Life 5 Dimension 5 Levels (EQ-5D-5L)
Quality of Life Scale
Immunoglobulin A
Immunoglobulin A serum levels
Immunoglobulin G
Immunoglobulin G serum levels
Immunoglobulin M
Immunoglobulin M serum levels
Interleukin-1
Interleukin-1 serum levels
Interleukin-6
Interleukin-6 serum levels
Anti-contactin-1
Anti-contactin-1 serum levels
Anti-neurofascin155
Anti-neurofascin155 serum levels
Anti-contactin-associated-protein1
Anti-contactin-associated-protein1 serum levels
Anti-neurofascin186
Anti-neurofascin186 serum levels
Anti-neurofascin140
Anti-neurofascin140 serum levels
Neurofilament Light Chain (NfL)
Neurofilament light chain (NfL) serum levels
Therapeutic Response
Share of patients with at least 10% improvement in CIDP score compared to baseline.

Full Information

First Posted
April 28, 2021
Last Updated
May 11, 2023
Sponsor
University of Ulm
Collaborators
Miltenyi Biomedicine GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT04881682
Brief Title
Immunoadsorption Versus Immunoglobulins for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Acronym
IVITOC
Official Title
Immunoadsorption Versus Immunoglobulins for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
March 1, 2026 (Anticipated)
Study Completion Date
March 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Ulm
Collaborators
Miltenyi Biomedicine GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CIDP

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immunoadsorption
Arm Type
Experimental
Arm Description
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)
Arm Title
Immunoglobulins
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Immunoadsorption
Intervention Description
see arm/group description
Intervention Type
Biological
Intervention Name(s)
Immunoglobulins
Intervention Description
see arm/group description
Primary Outcome Measure Information:
Title
CIDP Score
Description
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.
Time Frame
15 weeks
Title
Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Description
Standard clinical score for CIDP, quantifying disability.
Time Frame
15 weeks
Title
Oxford Muscle Strength Score (Medical Research Council, MRC)
Description
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).
Time Frame
15 weeks
Title
Vibration Score
Description
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).
Time Frame
15 weeks
Secondary Outcome Measure Information:
Title
CIDP Score
Description
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.
Time Frame
1, 7, and 13 weeks
Title
Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Description
Standard clinical score for CIDP, quantifying disability.
Time Frame
1, 7, and 13 weeks
Title
Oxford Muscle Strength Score (Medical Research Council, MRC)
Description
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).
Time Frame
16 weeks
Title
Vibration Score
Description
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).
Time Frame
16 weeks
Title
Pain
Description
Quantifying pain on a Visual Analog Scale between 0 (no pain) and 10 (maximum pain).
Time Frame
1, 7, 13, and 15 weeks
Title
N20 Latency
Description
N20 latency of Nervus medianus (both sides) in somatosensory evoked potentials (SEPs).
Time Frame
15 weeks
Title
P40 Latency
Description
P40 latency of Nervus tibialis (both sides) in somatosensory evoked potentials (SEPs).
Time Frame
15 weeks
Title
Nerve Conduction Velocity
Description
Nerve conduction velocities of clinically affected nerves as measured by electroneurography (ENG).
Time Frame
15 weeks
Title
Euro Quality of Life 5 Dimension 5 Levels (EQ-5D-5L)
Description
Quality of Life Scale
Time Frame
1, 7, 13, and 15 weeks
Title
Immunoglobulin A
Description
Immunoglobulin A serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Immunoglobulin G
Description
Immunoglobulin G serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Immunoglobulin M
Description
Immunoglobulin M serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Interleukin-1
Description
Interleukin-1 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Interleukin-6
Description
Interleukin-6 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Anti-contactin-1
Description
Anti-contactin-1 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Anti-neurofascin155
Description
Anti-neurofascin155 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Anti-contactin-associated-protein1
Description
Anti-contactin-associated-protein1 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Anti-neurofascin186
Description
Anti-neurofascin186 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Anti-neurofascin140
Description
Anti-neurofascin140 serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Neurofilament Light Chain (NfL)
Description
Neurofilament light chain (NfL) serum levels
Time Frame
1, 7, 13, and 15 weeks
Title
Therapeutic Response
Description
Share of patients with at least 10% improvement in CIDP score compared to baseline.
Time Frame
15 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johannes Dorst, Prof
Phone
+49 731 177 5285
Email
johannes.dorst@uni-ulm.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johannes Dorst, Prof
Organizational Affiliation
University of Ulm
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, University of Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Albert C Ludolph, MD, Prof.
Phone
+49-731-177-
Ext
1200
Email
albert.ludolph@rku.de
First Name & Middle Initial & Last Name & Degree
Albert C Ludolph, MD, Prof.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after de-identification (text, tables, and figures), as well as the study protocol will be available. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal. Proposals should be directed to johannes.dorst@uni-ulm.de; to gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at https://www.uniklinik-ulm.de/neurologie.html.
IPD Sharing Time Frame
3 months after publication until 5 years after publication
IPD Sharing Access Criteria
Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal.
IPD Sharing URL
https://www.uniklinik-ulm.de/neurologie.html

Learn more about this trial

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

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