The main objective of the study is to determine the PK and PD of IVIg during maintenance treatment in patients with CIDP. These data will be used to conduct a NONMEM analysis in relation to the dosage, frequency and batch of IVIg used. The secondary…
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Serum IgG levels determined over the duration of two subsequent IVIg courses at
standardized time points, before and after infusion.
Secondary outcome
Immunological parameters tested in order of high to low priority are: serum
levels of IgG subclasses, albumin, liver and kidney function parameters,
expression of Fc-receptors, genetic polymorphisms involved in IgG metabolism
(including polymorphisms in the IgG Fc-receptors), peripheral blood leukocytes,
cytokines, IgG glycoforms and IgG allotypes.
To confirm the clinical stability of the patients the following clinical
outcome measures will be monitored: hand grip strength (Vigorimeter), R-ODS and
R-FSS questionnaires.
Background summary
Intravenous immunoglobulin (IVIg) is an effective treatment for patients with
chronic inflammatory demyelinating polyneuropathy (CIDP). The therapeutic
effect, however, is usually transient and most patients require regular dosages
of IVIg at standard intervals during maintenance treatment for years or even
decades. The IVIg dosage and frequency is adapted to the clinical response of
the patient by *trial and error*. There are at present no biomarkers to monitor
the disease activity and treatment response. Individual patients who are
considered to be clinically stable are usually treated with a fixed IVIg
regimen, some however still slowly deteriorate (undertreatment). While other
patients still being treated with this costly therapy are in remission and do
not need regular IVIg administrations any longer (overtreatment). The required
dosage and interval of IVIg may differ between individual patients. Although
IVIg is in use for decades, very little is known about the pharmacokinetics
(PK) and pharmacodynamics (PD) (pharmacological profile) of IVIg treatment in
CIDP. In addition, the factors that influence the pharmacokinetics of IVIg and
determine the required dosages of IVIg in individual patients are unknown. A
previous study in our center suggests that the pharmacokinetics of IVIg
influence recovery of patients in a similar disease. Therefore serum IgG levels
may be used as a biomarker to predict and monitor the clinical efficacy of
IVIg.
Study objective
The main objective of the study is to determine the PK and PD of IVIg during
maintenance treatment in patients with CIDP. These data will be used to conduct
a NONMEM analysis in relation to the dosage, frequency and batch of IVIg used.
The secondary objective is to investigate which factors influence the
pharmacological profile of IVIg, including demographic, clinical and genetic
factors.
Study design
Observational cohort study.
Study burden and risks
Subjects will be asked to undergo a series of tests as well as a number of
blood drawings during a period of two subsequent IVIg courses (depending on
their schedule 4 - 8 weeks).
Blood samples will be drawn at standard time points during two subsequent IVIg
courses, including (1) 5 minutes before start of IVIg, treatment, (2) 15
minutes after finishing IVIg treatment, (3) 2 hours after IVIg, (4) 24 hours
after, (5) 2 days, (6) 7 days, (7) 14 days and in case of a treatment interval
of more than 3 weeks; (8) 21 days after IVIg. Proposed time points are not
entirely fixed and the definitive schedule will be in consultation with the
patient, to accommodate the sampling times as much as possible to the wishes of
the patient. Furthermore, some patients have a treatment interval of 2 weeks
or less. Time points will then be adjusted accordingly. EDTA blood sample for
extraction of DNA will be obtained before the first IVIg course after inclusion
in the study. The serum samples obtained 5 minutes before IVIg, and 15 minutes
and 2 hours after IVIg and the single EDTA blood sample will be obtained via
the peripheral catheter system. The other serum samples will be drawn by
venipuncture. The sampling at day 21 is performed only in the vast minority of
patients with an interval of IVIg maintenance treatment of 4 weeks or more.
Therefore, in the majority of patients the number of extra punctures, in
addition to the routine puncture to administer IVIg, will be 4 per treatment
course (8 for two courses). Hand grip strength (Vigorimeter) will be measured
before (at) every infusion by the nurse administrating the IVIg and during
certain time points (6-8) by qualified personnel of the Neurology department of
the Erasmus MC or nurses from the homecare treatment. During two occasions
patients are required to complete questionnaires (R-ODS and R-FSS). None of
these clinical outcome measures is painful or has a psychological burden for
the patient. The patients participating in the study will not directly profit,
but in the future we aim to optimize and monitor the treatment regimen of this
maintenance treatment for individual patients with CIDP.
Dr. Molewaterplein 50
Rotterdam 3015 GE
NL
Dr. Molewaterplein 50
Rotterdam 3015 GE
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of CIDP made by a consultant neurologist, fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical diagnostic criteria.
2. EMG findings compatible with the diagnosis CIDP showing peripheral nerve demyelination at least once during their illness. These findings should preferentially fulfill the electrodiagnostic criteria proposed by the European Inflammatory Neuropathy Cause and Treatment (INCAT) or EFNS/PNS.
3. Age >=18 years.
4. Patients require either to be on maintenance treatment with IVIg.
5. Signed informed consent by the patient.
Exclusion criteria
1. Known IgA deficiency or known allergic reaction to IVIg.
2. Known hereditary neuropathy or severe concomitant diseases such as HIV infection, Lyme disease, chronic active hepatitis, congestive heart failure, systemic lupus erythematosus, drug or toxin induced neuropathy, vasculitis, and malignancies.
3. Multifocal motor neuropathy (MMN), fulfilling the European Federation of Neurological Societies /Peripheral Nerve Society criteria.
4. IgM paraprotein with anti-myelin-associated glycoprotein (MAG) antibodies.
5. Atypical CIDP with pure sensory or persistent unifocal impairment or significant central nervous system involvement.
6. Severe known abnormalities in liver, kidney function or serum glucose level.
7. Concomitant treatment with prednisone.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004988-32-NL |
| CCMO | NL46993.078.13 |