Clinical trial NCT02111590: Immunoglobulin Dosage and Administration Form in CIDP and MMN
Official title: The Influence of Immunoglobulin Dosage and Administration on Development of Hemolytic Anemia and Variation on Muscle Strength in Patients With CIDP and MMN
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Multifocal Motor Neuropathy
Hemolytic Anemia
Keywords: Immunoglobulins, Intravenous
Immunoglobulins, Subcutaneous
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Octapharma Pharmazeutika Produktionsges.m.b.H.
First posted: 2014-04-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with CIDP or MMN in maintenance treatment with immunoglobulins

Brief summary: The aim of this study is to evaluate development of hemolysis and the variation in isokinetic muscle strength in two groups of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN)

1. Patients shifted from 3- or 6-weekly treatment with intravenous immunoglobulin (IVIG) to weekly treatment with subcutanoeus immunoglobulin (SCIG)
2. Patients shifted from SCIG treatment with Subcuvia® or Hizentra® to Gammanorm®.

Hypotheses

* During treatment with IVIG blood hemoglobin will fluctuate with a decline due to infusion, whereas it will remain stable during SCIG treatment without fluctuation
* Isokinetic muscle strength in affected muscle groups is more stable during treatment with SCIG than with IVIG
* Blood hemoglobin and changes in muscle strength is comparable during Subcuvia® or Hizentra® and Gammanorm® treatment

Detailed description: Due to planned switch of treatment with immunoglobulin at Department of neurology (Rigshospitalet) patients treated with IVIG will be shifted to treatment with SCIG with an unaltered dosage. The medication is administered at home two or three times weekly. IVIG is often administered every 3 to 6 weeks. All patients will be trained in managing the treatment with SCIG by a nurse from the neurological department. When the patient is able to manage the treatment regimen it can be done at home.

All patients will be evaluated eight times during the study period. Four times before and four times after shift of treatment.

Prior to participation the intervals will be standardized to 3 or 6 weeks giving an extra infusion for those with an interval of 3 weeks, i.e. patients on 4-week interval will be switched to 3-week interval while patients on 5-week interval will be switched to 6-week interval. The dose will be adjusted leading to an unchanged weekly dose of IVIG. All patients will be evaluated in connection to two IVIG infusions. For those receiving 3 infusions examinations will be executed before and 2 weeks after the first and last infusion. SCIG is initiated 2 weeks after the last IVIG infusion.

Patients on maintenance therapy with Subcuvia® or Hizentra® will be shifted to treatment with Gammanorm® according to guidelines from the Danish Healthcare Society, the weekly dose of immunoglobulin being unaltered. They will be evaluated 3 times (once before, at the time of shift of SCIG and once after).

All evaluations at each time point in both groups consist of measurement of isokinetic muscle strength of four affected muscle groups and blood sampling detecting blood hemoglobin and hemolytic parameters.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with CIDP or MMN fulfilling the EFNS/PNS criteria
* Maintenance treatment with IVIG or SCIG for at least 3 months
* Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study

Exclusion Criteria:

* Pure sensory or severe ataxic CIDP
* Other cause of neuropathy (incl. pressure neuropathy)
* Known history of adverse reactions to IgA in other products
* Exposure to blood or any blood product or plasma derivatives, other than Privigen, within the past 3 months prior to first infusion of Gammanorm
* Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products.
* Requirement of any routine premedication for IgG administration
* History of malignancies of lymphoid cells and immunodeficiency with lymphoma
* Severe liver function impairment (ALAT 3 times above upper limit of normal)
* Known protein-losing enteropathies or proteinuria.
* Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of Gammanorm
* Treatment with any investigational medicinal product within 3 months prior to first infusion of Gammanorm
* Medication interfering with hematopoiesis
* Other immunomodulation therapy than low dose steroid (Prednisolone \< 25 mg daily)
* Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of Gammanorm
* Known or suspected HIV, HCV, or HBV infection
* Pregnant or nursing women
* Planned pregnancy during course of the study

Primary outcomes:
measure: Variation in blood hemoglobin during treatment with IVIG and SCIG
timeFrame: Twenty weeks
Secondary outcomes:
measure: Variation in muscle strength during treatment with two preparations of SCIG
timeFrame: Twenty weeks
measure: Variation in muscle strength during treatment with IVIG and SCIG
timeFrame: Twenty weeks
measure: Variation in blood hemoglobin during treatment with two preparations of SCIG
timeFrame: Twenty weeks
Other outcomes:
measure: Comparison of Quality of life
timeFrame: Twenty weeks
Locations:
city: Copenhagen
country: Denmark
facility: Department of Neurology, Rigshospitalet
Study officials:
affiliation: Neuroscience Center, Rigshospitalet
name: Johannes Jakobsen, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Christiansen I, Markvardsen LH, Jakobsen J. Comparisons in fluctuation of muscle strength and function in patients with immune-mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin. Muscle Nerve. 2018 Apr;57(4):610-614. doi: 10.1002/mus.25967. Epub 2017 Nov 18.