|- candidate number||5291|
|- NTR Number||NTR1666|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-feb-2009|
|- Secondary IDs||2008-106 WC|
|- Public Title||The effect of Pyridostigmine on patients with CRPS-1.|
|- Scientific Title||Pyridostigmine: using a cholinesterase inhibitor to activate the cholinergic anti-inflammatory pathway in patients with CRPS-1.|
|- hypothesis||Pyridostigmine will activate the parasympathetic cholinergic anti-inflammatory pathway and therefore reduce inflammatory signs and symptoms in patients with complex regional pain syndrome. |
|- Healt Condition(s) or Problem(s) studied||Complex Regionaal Pain Syndrome (CRPS), Central neuropathic pain, Neurogenic inflammation|
|- Inclusion criteria||Patients with CRPS-1 according to Veldman criteria, autonomic alterations like hypo/hyper hydrosis, altered hair/nail growth, unsatisfactory results of standard treatment, ability to give informed consent, age >18.|
|- Exclusion criteria||CRPS-1 or other condition on contralateral extremity, asthma, cardiac problems, hyperthyroidism, epilepsy, parkinson, kydney dysfunction, severe psychiatric dysfunction, history of digestive tract operation or ulcers, active malignant disease, other chronic pain syndrome, use of anti-cholinergic medication.|
|- mec approval received||no|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-apr-2009|
|- planned closingdate||1-sep-2009|
|- Target number of participants||10|
|- Interventions||Pyridostigmine in an individual dosage.|
|- Primary outcome||1. Pain (VAS score);|
2. Motor funcion (AROM);
|- Secondary outcome||1. Autonomic functioning;|
2. Blood analysis on oxidative stress;
3. Acetylcholine status.
|- Timepoints||1. 3 weeks titration phase, with continuous evaluations;|
2. Then, week 4, 6, 8, 10, 14.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. S.G.L. Fischer|
|- CONTACT for SCIENTIFIC QUERIES||Drs. S.G.L. Fischer|
|- Sponsor/Initiator ||TREND|
(Source(s) of Monetary or Material Support)
|- Brief summary||Pyridostigmine: using a Cholinesterase Inhibitor to activate the Cholinergic Anti-Inflammatory Pathway in patients with CRPS-I. |
Background of the study:
Complex regional pain syndrome type I (CRPS-I) is a painful and disabling condition which can develop after trauma, such as wrist fracture, distortion or operation, but without preceding incident. CRPS-I is characterized by pain and sensory abnormalities, oedema and sudomotor dysfunction, colour change, limited range of motion and autonomic disturbances (for example excessive sweating of the affected limb). Another symptom is that pain will get worse when the extremity is used more.
Several pathological mechanisms have been suggested to play a role in the development of CRPS-1. This study is based on the assumption that CRPS-1 is caused by neurogenic inflammation, in which free radicals are involved. Although this can not explain all the symptoms we find in this pain syndrome.
Neurogenic inflammation starts as a natural process when peripheral trauma occurs. The following immune reaction starts a cascade of cytokines and a local inflammatory response. The human immune system must also be capable to down-regulate this reaction when a trauma has healed to minimize the local damage obtained by this inflammation. For this regulation two pathway are believed to play a part, the “classical” humoral immunologic pathway and the cholinergic pathway.
The cholinergic pathway is an interesting pathway for therapeutic use, because it is regulated by nerves and thereby a fast way of 'communication'. A key factor of the cholinergic pathway is the neurotransmitter Acetylcholine (ACh) which is excreted by stimulation of the nervus vagus and communicates with the local immune cells (eg. macrophages) by Acetylcholine receptors (AChR), which are expressed on those immune cells. The activated Acetylcholine receptors inhibit the production of cytokines and thereby modulate the inflammation. As a therapeutical options the ACh has to be raised around the immune cells. A possibility to reach a higher level of ACh is to inhibit the Acetylcholinesterase and thereby lower the re-uptake of ACh. In this study a higher level of ACh will be accomplished by the use of Pyridostigmine (cholinesterase inhibitor).
Objective of the study:
The effect of Pyridostigmine (cholinesterase inhibitor) on inflammatory signs as pain, temperature, swelling and functional status of the extremity measured according to TREND protocol (app 1).
Are the patients treated with Pyridostigmine clinically getting better and have less pain?
Side-effects of Pyridostigmine measured by PBSES (appendix 2)
This study will be a single-subject-study in which we will follow 10 patients with CRPS-I and evident signs of inflammation (Veldman-criteria). It will be a study with a baseline measurement (A), a titration fase of 3 to 6 weeks and an actual therapeutical fase (B). After 12 weeks of treatment Pyridostimine will be stopped and a new base line will be measured at 14 weeks (A) (A-titration fase-B-A). Further follow-up will take place after 6 months and 12 months (app 3).
|- Main changes (audit trail)|
|- RECORD||9-feb-2009 - 14-sep-2009|