|Pilot Study on Safety and Efficacy of the Non-Invasive Transcranial Stimulation to Relieve Neuropathic Pain in Patients with CRPS
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.
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
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
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
Serious health problems other than CRPS (e.g. uncontrolled
hypertension, uncontrolled diabetes)
Pain/painful conditions unrelated to CRPS
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
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
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.
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June 28, 2007