Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Overview
- Phase
- Phase 2
- Intervention
- Deep brain stimulation
- Conditions
- Neuralgia
- Sponsor
- University of Aarhus
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
Chronic neuropathic pain affects millions of individuals worldwide. It causes marked reduction of health, utility and quality of life and represents a considerable economic burden to society due to loss of work capacity and large treatment expenses. The proposed project will explore new and rational methods for deep brain stimulation treatment of patients with severe chronic neuropathic pain, resistant to conventional treatment. Deep brain stimulation is a neurosurgical procedure in which a small stimulating electrode is implanted into deep brain areas. Furthermore, we will utilize new positron emission tomography neuroimaging and a new prototyped technology, called targeted transcranial magnetic stimulation, to predict the outcome of deep brain stimulation and localize brain regions with maximum symptom relief for each patient. This will optimize the selection of patients for deep brain stimulation and provide a rational customized choice of brain target for each patient, without surgical intervention. Novel techniques will be validated on healthy volunteers and at the same time provide new insights into the mechanisms underlying brain stimulation and pain perception. The project has great clinical impact, potential for innovative development and industrial spin-out, facilitates exchange for Danish research talents and senior researchers with Stanford University and California Pacific Medical Research Institute in San Francisco, and unites world leading experts in pain research and clinical treatment to achieve its goals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •General inclusion criteria (case and control):
- •No gender criteria
- •Age \> 25 years.
- •Legal competency.
- •Ability to comply with the proposed protocol schedule.
- •Stability of chronic medical diseases.
- •A negative validated pregnancy test for fertile female participants prior to project enrolment.
- •Use of validated anti-conception for fertile female participants
- •Case-specific inclusion criteria:
- •Well-defined neuropathic pain \[21\].
Exclusion Criteria
- •General exclusion criteria:
- •Pregnancy or nursing.
- •Cognitive impairment.
- •Alcohol or drug abuse
- •Severe psychiatric disorders.
- •Allergies towards compounds used in the trial, such as PET tracers, Capsaicin, etc. Other significant medical allergies.
- •Severe medical disorders
- •Neurodegenerative disorders
- •Severe cerebrovascular diseases and risk-factors, malignant hypertension, vascular abnormalities.
- •Prior intracranial surgery
Arms & Interventions
Sham-DBS
Only patients. Inactive deep brain stimulation for the initial three months following implantation.
Intervention: Deep brain stimulation
Sham-DBS
Only patients. Inactive deep brain stimulation for the initial three months following implantation.
Intervention: Cervel Neurotech, Multi-coil TMS
Sham-DBS
Only patients. Inactive deep brain stimulation for the initial three months following implantation.
Intervention: 11C-Carfentanil
Active DBS
Only patients. Active deep brain stimulation for the initial three months following surgery.
Intervention: Deep brain stimulation
Active DBS
Only patients. Active deep brain stimulation for the initial three months following surgery.
Intervention: Cervel Neurotech, Multi-coil TMS
Active DBS
Only patients. Active deep brain stimulation for the initial three months following surgery.
Intervention: 11C-Carfentanil
TMS and PET imaging
This experiment includes all participants (cases and controls). Each subject will undergo both active and sham stimulation (cross-over) with Cervel Neurotech Multi-coil TMS and related test/re-test PET imaging with 11C-Carfentanil. Only patients will proceed into deep brain stimulation experiments.
Intervention: Cervel Neurotech, Multi-coil TMS
TMS and PET imaging
This experiment includes all participants (cases and controls). Each subject will undergo both active and sham stimulation (cross-over) with Cervel Neurotech Multi-coil TMS and related test/re-test PET imaging with 11C-Carfentanil. Only patients will proceed into deep brain stimulation experiments.
Intervention: 11C-Carfentanil
Outcomes
Primary Outcomes
Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
Time Frame: Assessment after 3 and 12 months of active stimulation
We will measure the changes in pain ratings upon deep brain stimulation of the dorsal anterior cingulate gyrus. Results will be based on the numerical rating scale and validated questionnaires. We will compare active and sham stimulation and changes upon activation of initial sham-stimulation.
Predictive values of PET imaging and transcranial magnetic stimulation on deep brain stimulation outcome
Time Frame: Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)
Individuals will be classified according to PET activity/no-activity and positive/null-negative outcome of transcranial magnetic stimulation. We will correlate the effect of deep brian stimulation to these categories and evaluate their predictive values.
Secondary Outcomes
- Effect of deep brain stimulation on cingulate opioid binding and blood flow.(After 3 and 12 months of active deep brain stimulation)
- Pain relief upon individualized deep brain stimulation(After 3 and 12 months of active deep brain stimulation)