Double-blind randomised placebo-controlled cross-over study to investigate the safety and effectiveness of intrathecal glycine on pain and dystonia in Complex Regional Pain Syndrome type 1.

Introduction:

A large proportion of chronic patients with complex regional pain syndrome type 1 (CRPS I) suffer from both neuropathic pain and dystonia.
Findings from neurophysiological and intrathecal baclofen studies highlight an impaired inhibitory neurotransmission.
Since glycinergic neurotransmission plays an important inhibitory role in afferent and motor processing, glycine administration may offer new options for the treatment of both pain and movement disorders in patients with CRPS I.


Aim of the study:

- Primary aim of the study is to evaluate the safety of intrathecal glycine (ITG) in CRPS I patients.

- Secondary aim is to study the effectiveness of ITG treatment during 4 weeks (in an increasing dose schedule).


SUBJECTS:

Subjects will be male or female out-patients, at least 18 years of age, with a clinical diagnosis of CRPS I related dystonia who are referred to the movement disorders out-patients' clinic of the department of Neurology at the Leiden University Medical Centre (LUMC) for intrathecal baclofen treatment.


Methods:

The ITG study is a double-blind randomised placebo-controlled cross-over study.
For future intrathecal baclofen treatment, in all patients a programmable pump for continuous intrathecal administration is implanted.
Study treatment is started at a dosage of 8/21 mL/24 hours and will be weekly increased with 8/21 mL/24 hours.
In case of adverse events, dose will be halved (and if needed repeated) or stopped, depending on the opinion of the investigators.
Safety and efficacy are assessed by means of standardized evaluation.
Patients are assessed 2 weeks before pump implantation and during both treatments at day 1, day 2, day 4, day 8, day 15, day 22 and day 29.

A large proportion of chronic patients with complex regional pain syndrome type 1 suffer from both neuropathic pain and dystonia. Findings from neurophysiological and intrathecal baclofen studies highlight an impaired inhibitory neurotransmission. Since glycinergic neurotransmission plays an important inhibitory role in afferent and motor processing, glycine administration may offer new options for the treatment of both pain and movement disorders in patients with CRPS I.

N/A

For future intrathecal baclofen treatment, in all patients a programmable pump for continuous intrathecal administration (SynchroMed® pump, Medtronic, Minneapolis MN, USA, 40 mL reservoir) and a lumbar reservoir for cerebrospinal fluid sampling will be implanted.
Each subject receives two treatments:
1. 2.1% glycine solution during 4 weeks and
2. natrium chloride 0.9% during 4 weeks (placebo).
Study treatment is started at a dosage of 8/21 mL/24 hours (during treatment with glycine 2.1% this corresponds to 8 mg/24 hours) and will be weekly increased with 8/21 mL/24 hours.
There is a tapering and wash-out period after each treatment: tapering in 1 week (3 equal dose decreases with an interval of 48 hours, e.g. monday 22, wednesday 12 and friday 0 mg/24 hours) and wash-out in 1 week.
Treatment is started on mondays.