Combined Cingulate and Thalamic DBS for Chronic Refractory Chronic Pain

Study Overview
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Brief Summary
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Deep brain stimulation (DBS) of the sensory thalamus has been proposed for 40 years to treat medically refractory neuropathic pain, but its efficacy remains partial and unpredictable. Recently, bilateral DBS of the dorsal anterior cingulate cortex (ACC), a brain region involved in the integration of the affective and cognitive aspects of pain, has been successively proposed to treat few patients suffering from refractory chronic pain, by decreasing the emotional impact of their chronic pain. ACC-DBS could be an alternative or complementary approach to thalamic DBS in these patients, but the consequences of chronic dACC-DBS on cognition and affects have not been studied specifically. The primary objective is to evaluate the feasibility and safety of bilateral ACC-DBS combined with unilateral thalamic DBS in patients suffering from chronic unilateral pain, refractory to medical treatment. Secondary objective will evaluate the efficacy of this combined DBS compared to thalamic DBS only.

Detailed Description
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Chronic pain represents a major personal and societal burden, especially for medically resistant patients. Deep brain stimulation (DBS) of the sensory thalamus has been proposed for 40 years to treat medically refractory neuropathic pain, but its efficacy remains partial and unpredictable. Recently, bilateral DBS of the dorsal anterior cingulate cortex (ACC), a brain region involved in the integration of the affective, emotional and cognitive aspects of pain, has been successively proposed to treat few patients suffering from refractory chronic pain. In a pilot study, 16 patients treated by ACC-DBS experienced a significant improvement of their quality of life despite a slight decrease of their pain intensity, by improving the affective and emotional impacts of their chronic pain. ACC-DBS could be an alternative or complementary approach to thalamic DBS in these patients. However the consequences of chronic dACC-DBS on cognition and affects have not been studied specifically. The primary objective of this study is to evaluate the feasibility and safety of bilateral ACC-DBS combined with unilateral thalamic DBS in patients suffering from chronic unilateral pain, refractory to medical treatment. Secondary objective will evaluate the efficacy of this combined DBS compared to thalamic DBS only

Official Title
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Treatment of Chronic Refractory Pain by Combined Deep Brain Stimulation of the Anterior Cingulum and Sensory Thalamus: a Feasibility and Safety Study

Conditions
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Chronic Refractory Neuropathic Pain

Intervention / Treatment
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* Procedure: Deep brain Stimulation of cingulum anterior


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients (age 18-70 years old) suffering from chronic (duration >1 year) unilateral neuropathic pain severe (VAS score >6/10) with high emotional impact (HAD subscores > 10) considered as resistant to medication specific to neuropathic pain at sufficient doses and durations (including at least antiepileptics and antidepressants) and not sufficiently improved by rTMS and relevant surgical solutions. Non inclusion criteria: previous history of stroke, cognitive impairment (MMSE score <24), DSMIV axis I psychiatric disorder, contra-indication to surgery, anesthesia or MRI; patient responder to rTMS,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBS-ACC ON<br>Start of stimulation of the DBS-ACC: On the first period, between M4 and M7, the DBS-ACC is ON and the second period, between M7 and M10 is OFF | Procedure: Deep brain Stimulation of cingulum anterior<br>* The Deep brain Stimulation of cingulum anterior is alternatively ON and OFF while Thalamic stimulation is ON<br>|
| Experimental: DBS-ACC OFF<br>Start of stimulation of the DBS-ACC: On the first period, between M4 and M7, the DBS-ACC is OFF and the second period, between M7 and M10 is ON | Procedure: Deep brain Stimulation of cingulum anterior<br>* The Deep brain Stimulation of cingulum anterior is alternatively ON and OFF while Thalamic stimulation is ON<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of serious adverse events. | description of serious adverse events | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Feasibility of ACC-DBS: success the process of surgical intervention | Feasibility of ACC-DBS will be evaluated by the proportion of patients undergoing with success the process of surgical intervention Safety will be evaluated by neurological examination | Day 0 | 
| Feasibility of ACC-DBS : neurological success of the process of chronic stimulation | neurological success of the process of chronic stimulation will be evaluated by the neurological examination | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Feasibility of ACC-DBS : psychiatric success of the process of chronic stimulation | psychiatric success of the process of chronic stimulation will be evaluated by the psychiatric assessment | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Feasibility of ACC-DBS : cognitive success of the process of chronic stimulation | cognitive success of the process of chronic stimulation will be evaluated by the cognitive assessment | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of ACC-DBS : change of pain intensity | Efficacy of ACC-DBS will be evaluated by pain intensity (VAS) | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Efficacy of ACC-DBS : change of pain intensity | Efficacy of ACC-DBS will be evaluated by pain intensity (Brief Pain Inventory) | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Efficacy of ACC-DBS : change of pain intensity | Efficacy of ACC-DBS will be evaluated by pain intensity (McGill Pain Questionnaire) | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Efficacy of ACC-DBS : change of quality of life by SF-36 | Efficacy of ACC-DBS will be evaluated by quality of life (SF36). | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 | 
| Efficacy of ACC-DBS : change of quality of life by EQ-5D | Efficacy of ACC-DBS will be evaluated by quality of life (EQ5D). | Day 0, Month 1, Month 4, Month 7, Month 10, Month 22 |