Dose response trial of IV immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy

In clinical practice CIDP patients are being treated with different dosages and
different infusion intervals of IVIg. The optimum dosage and intreval has not
been investigated IgG is the major component of IVIg and is probably
responsible for most of the immune-modulating effects.
It is unknown how IVIg should be administered for optimal immunomodulation;
whether keeping the plasma level of IgG high for prolonged periods is better
than spiking the immune system intermittently with high doses of IVIg. The
purpose of maintenance IVIg treatment in CIDP is to maintain a constant serum
IgG level. A high peak dose may result in greater catabolism of IgG which might
be avoided by giving smaller doses more often. Shortening the interval between
IVIg infusions results in a higher IgG trough level which appears to correspond
to clinical efficacy. The pharmacokinetics of IgG differ when lower dosages are
given more frequently resulting in lower peaks and higher troughs which may be
preferable to a lower frequency high dosage regimen. It is known that the
treatment frequency cannot be lowered in CIDP patients. More frequent dosing
leads to more stable IgG levels without high peak levels which have been held
responsible for the systemic side effects.

The primary objective is:
1. To investigate whether high frequency low dosage IVIg treatment is more
effective than low frequency high dosage as maintenance treatment for CIDP.
Secondary objectives are:
2. To investigate whether high frequency low dosage of IVIg results in less
adverse events compared to low frequency high dosage.
3. To prove that high frequency low dosage of IVIg results in higher IgG trough
levels than low frequency high dosage.

Randomised double-blind controlled crossover study. Two dosing schedules of the
same drug are being compared. Placebo will be only added to maintain the
blind.

intervention group/arm:
4 infusions of IVIg of half the normal dosage (with placebo added to maintain
the total volume) and half the interval (double the frequency).

Control group/arm:
2 infusion of IVIg according to the normal; dose and intreval as well as two
sham (placebo) infusions.

The total amount of IVIg given during the whole double-blind phase will remain
the same in both groups. As this is a crossover study all pateints will receive
both treatment schedules once.

Due to the fact that patients are treated in the trial with the same drug as
before start of the trial and the fact that the total amount (grams) of IVIg
over time will be the same as before start of the trial there are no risks to
be expected from participation of this trial. A burden for the patients is that
patients receive four extra infusions during the trial. Before and after very
infusion a blood sample will be drawn. this blood sample will be taken from the
infusion needle therefore no extra venapunction is needed. when pateints give
additional permission once a blood sample will be drawn from the infusion
needle for DNA examination and 2 days after every infusion a blood sample will
be drwan (venapunction) which can be done at the patients home. Furthermore
patients will be asked to complete some questionnaires before every infusion.