The Effect of Transcranial Direct Current Stimulation (t-DCS) On the P300 Component of Event-Related Potentials in Patients With Chronic Neuropathic Pain Due To CRPS or Diabetic Neuropathy

Study Overview
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Brief Summary
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This is a controlled trial designed to determine short- and long-term effects of repeated tDCS on the P300 component of event-related evoked potentials in patients with chronic neuropathic pain due to Complex regional Pain Syndrome (CRPS) or diabetic neuropathy as compared with healthy subjects.

Official Title
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The Effect of Transcranial Direct Current Stimulation (t-DCS) On the P300 Component of Event-Related Potentials in Patients With Chronic Neuropathic Pain Due To Complex Regional Pain Syndrome (CRPS) or Diabetic Neuropathy-A PILOT, DOUBLE-BLIND, SHAM-CONTROLLED, CROSS-OVER STUDY

Conditions
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Diabetic Neuropathies, Complex Regional Pain Syndrome Type II, Resistant Peripheral Neuropathic Pain, Chemotherapy Induced Pain Neuropathy

Intervention / Treatment
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* Device: TDCS/sham procedure on five consecutive days


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An affected upper limb or lower limb Diagnosed as : Diabetic neuropathy, Complex Regional Pain Syndrome (CRPS), Chemotherapy Induced Pain Neuropathy (CIPN), Peripheral Neuropathy. Have not responded to at least two medications of the following groups: Opioids. Tricyclics, SSRI, SNRI, Pregabalin, Gabapentin, Anticonvulsants. Positive LANSS or CRPS criteria as follows: Continuing pain which is disproportionate to any inciting event or for CRPS diagnosis. Must report at least one symptom (symptoms here are reports by subject) in each of the four following categories: sensory, vasomotor, sudomotor/edema, motor/trophic. Must display at least one sign (signs here refer to objective observation/testing) in in each of the four following categories: sensory, vasomotor, sudomotor/edema, motor/trophic; Must meet resistant neuropathic pain criteria - pain that is neuropathic in characters that at least two neuropathic medications not from the same group have been tried for at least a month without improvement or severe side-effects were experienced. Resistant neuropathic pain with a score for average pain in the last 24 hours ≥4 on a numeric scale 0-10 tDCS naive Exclusion Criteria: Serious health problems other than CRPS or resistant neuropathic pain (e.g. uncontrolled hypertension, uncontrolled diabetes, heart failure) Pain/painful conditions unrelated to CRPS or neuropathic pain Pregnancy History of seizures/epilepsy Implanted device (e.g. pacemaker) Active illicit drug/alcohol abuse Unable to follow directions or complete tools in Hebrew Previous exposure to tDCS stimulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1-CRPS<br>10 tDCS naïve patients with CRPS-related neuropathic pain in upper limb | Device: TDCS/sham procedure on five consecutive days<br>* The latency and amplitude of P300, subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined at before and 15 min and 120 min after the 1st and 5th tDCS/sham procedure, To receive tDCS/sham treatment, two electrodes will be placed on the patient´s skull (for details see section Methods) and the patient will rest for 5 min. After that, the patient will receive 20 minutes of 2 mA tDCS/sham. Subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined before-, 15 min after and 120 min after each tDCS/Sham procedure. At the 1st and 5th tDCS/Sham session, the latency and amplitude of P300 will be determined before-, 15 min after and 120 min after the tDCS/sham procedure.<br>|
| Experimental: 2-DN<br>20 tDCS naïve patients with diabetic neuropathy | Device: TDCS/sham procedure on five consecutive days<br>* The latency and amplitude of P300, subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined at before and 15 min and 120 min after the 1st and 5th tDCS/sham procedure, To receive tDCS/sham treatment, two electrodes will be placed on the patient´s skull (for details see section Methods) and the patient will rest for 5 min. After that, the patient will receive 20 minutes of 2 mA tDCS/sham. Subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined before-, 15 min after and 120 min after each tDCS/Sham procedure. At the 1st and 5th tDCS/Sham session, the latency and amplitude of P300 will be determined before-, 15 min after and 120 min after the tDCS/sham procedure.<br>|
| Experimental: 3-RPNP<br>20 tDCS naïve patients with resistant peripheral neuropathic pain | Device: TDCS/sham procedure on five consecutive days<br>* The latency and amplitude of P300, subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined at before and 15 min and 120 min after the 1st and 5th tDCS/sham procedure, To receive tDCS/sham treatment, two electrodes will be placed on the patient´s skull (for details see section Methods) and the patient will rest for 5 min. After that, the patient will receive 20 minutes of 2 mA tDCS/sham. Subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined before-, 15 min after and 120 min after each tDCS/Sham procedure. At the 1st and 5th tDCS/Sham session, the latency and amplitude of P300 will be determined before-, 15 min after and 120 min after the tDCS/sham procedure.<br>|
| Experimental: 4-CIPN<br>10 tDCS naïve patients with CIPN-Chemotherapy Induced Pain Neuropathy patients | Device: TDCS/sham procedure on five consecutive days<br>* The latency and amplitude of P300, subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined at before and 15 min and 120 min after the 1st and 5th tDCS/sham procedure, To receive tDCS/sham treatment, two electrodes will be placed on the patient´s skull (for details see section Methods) and the patient will rest for 5 min. After that, the patient will receive 20 minutes of 2 mA tDCS/sham. Subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined before-, 15 min after and 120 min after each tDCS/Sham procedure. At the 1st and 5th tDCS/Sham session, the latency and amplitude of P300 will be determined before-, 15 min after and 120 min after the tDCS/sham procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the amplitude of P300 |  | 15 min after and 120 min after the 1st tDCS, 15 min after and 120 min after the 5st tDCS, and at the follow up 1 week after the 5th tDCS. | 
| Changes in the Latency of P300 |  | 15 min after and 120 min after the 1st tDCS, 15 min after and 120 min after the 5st tDCS, and at the follow up 1 week after the 5th tDCS. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pain Intensity-will be calculated as the difference in scores on the 11-point numerical pain rating scale (0-10) |  | 15 min after and 120 min after each tDCS stimulation | 
| Changes in Pain Thresholds for Tactile and Thermal Stimuli will be calculated as the difference between ratings obtained form pain threshold measurements before- and after tDCS |  | 15 min after and 120 min after each tDCS stimulation |