The influence of different flow rates of intrathecal baclofen infusion on dystonia and pain in Complex Regional Pain Syndrome type 1

A double-blind randomized two-period cross-over study will be used to analyse the efficacy of a 4-times higher flow rate of ITB on dystonia and pain in CRPS I.

Primary outcomes are severity of pain and dystonia using a NRS.

Secondary outcomes are:

1. Efficacy as evaluated by dystonia severity (Burke-Fahn-Marsden scale), patient¡¯s preference (PPQ), and global impression of improvement after each treatment (global impression scale).

2. Safety of the procedure as evaluated by the occurrence of adverse events.

To study the difference in outcome between both flow rates, a paired samples t-test (or Wilcoxon Signed Rank Test in case of non-normal distribution) will be used. Differences are considered significant if the p values are ¡Ü 0.05. The frequency and severity of adverse events will be compared between both regimes.

The infusion of intrathecal baclofen using higher flow rates results in more extensive intrathecal distribution, hence benefits pharmacodynamic properties of baclofen

1. Every day from last week before until 5 weeks after first switch of ITB concentration (NRS-score)

2. Day 1, 14, 21 and 35 after first switch of ITB concentration (history, examination, Burke-Fahn-Marsden score, Global Impression Score, Patient Preference Questionnaire)

1. Before the start of the study all patients have received continuous ITB with a concentration of 3000 µg/ml.
The study starts with replacing the current substitution of 3000 µg/ml baclofen by randomly allocated 3000 µg/ml or 750 µg/ml concentrations of ITB. To maintain a fixed daily dose of ITB, flow rates will be adjusted accordingly to the administered concentration (3000 µg/ml - no change; 750 µg/ml ¨C 4-fold increase).

2. During a 2 week period, the first allocated flow rate will be used.
The following week, baclofen will be administered using the baseline flowrate in an unblinded manner (patient & rater) to minimize potential consequences of any carry-over effect.

Subsequently, the following 2 week period the second allocated flow rate will be used after which all patients will continue on open ITB using the baseline flow rate.

3. Changing the different flow rates requires a special switch procedure, which will be carried out by a physician not involved in the assessments of the patients.

4. If a baclofen-related side-effect occurs, the flow rate will be reduced to a lower rate, depending on the severity of the side-effect.

5. Clinical observation will take place for at least 24 hours after replacing concentrations.