People who have CRPS-related pain in the upper or lower limb may be eligible for an outpatient research study at Beth Israel Medical Center, in New York City.

To check whether you may be eligible for the study, please call 212-420-3823 (Dr Helena Knotkova). Leave your full name and phone number, and your call will be returned in 48 hours. The study personnel will explain the study procedures; answer questions you might have, and pre-screen by phone your preliminary eligibility for the study.

This study is funded in part by RSDSA.

Abstract

Previous research revealed that pain in CRPS patients is associated with cortical reorganization, i.e. pathological changes in the somatotopic organization and excitability of the motor and somatosensory cortex (Eisenberg et al., 2005; Schwenkreis et al., 2003; Pleger et al., 2005; 2005; and others). As studies in patients with CRPS and other symptomes featuring neuropathic pain have shown that reversal of pathological cortical changes back to normal is accompanied by pain relief (Maihöfner et al., 2003, 2004), modulation of cortical excitability seems to be a promising therapeutic approach to aleviate neuropathic pain.
The purpose of the study is to determine the efficacy of a new non-invasive completely painless technique called trancranial direct current stimulation (tDCS), to alleviate pain and sensory abnormalities in patients with CRPS. The investigators predict that 1) the real tDCS stimulation at current intensity 2mA, but not sham(placebo), will result in a significant pain relief, 2) pain relief will be better after repetitive stimulation in comparison with a single tDCS session; 3) tDCS will improve sensory abnormalities (allodynia, hyperalgesia) and motor function of the affected limb.

The tDCS treatment is non-invasive (no surgical procedures are needed) and it is completely painless. TDCS is based on stimulation of selected parts of brain with direct electrical current of very low intensity of 2 milliampers (mA), using two electrodes placed on the skull. Safety of tDCS has been tested in several research studies, and it has been shown that tDCS is safe and it does not negatively affect brain functions. In 1999, the FDA decided that the tDCS device (the Phoresor® II Auto from IOMED® Salt Lake City, Utah 84120 USA) did not carry significant risk and was exempt from the Investigational Device Equipment requirements.

The trial has two parts (Phase 1 and Phase 2). Patients who qualify for the study will enter Phase 1. Phase 1 of the study is conducted as a double-blind study, which means that neither the patient nor the investigator will know if the patient receive the real tDCS treatment or placebo. The reason for the "double-blinding" is to test the effect of tDCS in a way that will not be influenced by anyone's opinions or expectations. To increase the chance that patients will receive the real tDCS in the Phase 1 of the study, the randomization will be done in ratio 2:1 in favor of the real tDCS. It means the patient's chance that he/she will be in a group receiving the real tDCS is about 66%. If the patient get randomized to the group receiving placebo, he/she still can get the real tDCS treatment in the Phase 2 of the study. If the pain does not improve in the randomized double-blind Phase 1, he/she will be eligible to participate in Phase 2 of the study and will receive the real tDCS. If the patient's pain improves in the randomized Phase 1 of the study, he/she will not participate in Phase 2.

To participate in the study, patients have to meet following Inclusion/Exclusion criteria:

Inclusion Criteria

•Affected an upper or lower limb
•Spontaneous pain with a score for "worst pain in the last 24 hours" >4 on a numeric scale 0-10
•Must meet CRPS diagnostic criteria (Sandroni et al., 2003) with the application of the IASP criteria as adapted by Bruehl et al (1999):
1) Continuing pain which is disproportionate to any inciting event
2) Must report at least one symptom (symptoms here are reports by subject) in each of the four following categories: sensory, vasomotor, sudomotor, motor/trophic
3) Must display at least one sign (signs here refer to objective observation/testing) in each of the four following categories: sensory, vasomotor, sudomotor, motor/trophic

Exclusion Criteria

• Serious health problems other than CRPS (e.g. uncontrolled hypertension, uncontrolled diabetes)
•Pain/painful conditions unrelated to CRPS
•Pregnancy
•History of seizures/epilepsy
• Any implanted devices (e.g. a cardiostimulator, etc)
• Active illegal drug/alcohol abuse
• Unable to follow directions or complete tools in English

Patients who will meet Inclusion/Exclusion criteria and decide to participate will be enrolled into the study. After a baseline evaluation of pain, somatosensory abnormalities, and motor function at the baseline visit, patients will undergo 5 sessions of 20 min of 2 mA tDCS real stimulation (group A) or sham (group B) on 5 consecutive days, Mon-Fri. Patients' pain, somatosensory abnormalities, and motor function of the affected vs unaffected upper limb will be evaluated before and after each session. To receive the tDCS/sham treatment, two saline soaked electrodes will be placed non-invasively over the skull, one at position C3 (see the International EEG Classification) of hemisphere contralateral to the affected limb, the other electrode will be placed over the orbita ipsilateral to the affected limb.

Two weeks after the last tDCS/Sham session of Phase 1, patients will come for the Phase1-Completion-Visit. All patients whose pain will not improve at least by 3 of 10 points on the numerical pain rating scale at the end of the double-blind Phase 1 as compared with the Baseline, will continue in the open-label Phase 2 and will receive the real tDCS treatment, i.e. 20 min of tDCS at 2 mA, in 5 sessions on 5 consecutive days, Mon-Fri. After the last tDCS session, patients will undergo the Phase2-Completion-Visit. Phase 2 has to be completed in 1 month after the end of Phase 1.

The initial visit and the completion visit will last about one hour, the visits with the tDCS stimulation will last about two hours.

Through the course of the study, patients will keep Daily Diaries, i.e. daily records on pain, rescue medication and changes of health status.
Participation in this study does not require any changes in patient's medication regimen.

Selected Literature:

Eisenberg E, Chystiakov AV, Yudashkin M, Kaplan B, Hafner H, Feinsod M. Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study. Pain. 2005;113:99-105.

Fregni F, Boggio PS, Lima MC, et al. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006.

Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006.

Hummel F, Cohen LG. Improvement of motor function with noninvasive cortical stimulation in a patient with chronic stroke. Neurorehabil Neural Repair. 2005;19:14-19.

Krause P, Foerderreuther S, Straube A. Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand. Letter to the editor. Neurol.2004;62:1654-1655.

Maihofner CCA, Handwerker HO,Neundorfer B, Birklein F. Patterns of cortical reorganization in complex regional pain syndrome. Neurol. 2003;61:1707-1715.

Maihofner C, Foster C, Birklein F, Neundorfer B, Handwerker HO. Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study. Pain. 2005;114(1-2):93-103.

Maihofner CCA, Handwerker HO, Neundorfer B,Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurol. 2004;63(4):693-701.

Nguyen JP, Lefaucher JP, Le Guerinel C, et al. Motor cortex stimulation in the treatment of central and neuropatic pain. Arch of Med Research. 2000;31(3):263-265.

June 28, 2007